195 results on '"rita cortesi"'
Search Results
2. Manganese-Loaded Liposomes: An In Vitro Study for Possible Diagnostic Application
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Maddalena Sguizzato, Petra Martini, Francesca Ferrara, Lorenza Marvelli, Markus Drechsler, Giovanni Reale, Francesca Calderoni, Federica Illuminati, Francesca Porto, Giorgia Speltri, Licia Uccelli, Melchiore Giganti, Alessandra Boschi, and Rita Cortesi
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manganese ,liposomes ,diagnostic application ,MEMRI ,contrast agents ,Organic chemistry ,QD241-441 - Abstract
The present study investigates the possible use of manganese (Mn)-based liposomal formulations for diagnostic applications in imaging techniques such as magnetic resonance imaging (MRI), with the aim of overcoming the toxicity limitations associated with the use of free Mn2+. Specifically, anionic liposomes carrying two model Mn(II)-based compounds, MnCl2 (MC) and Mn(HMTA) (MH), were prepared and characterised in terms of morphology, size, loading capacity, and in vitro activity. Homogeneous dispersions characterised mainly by unilamellar vesicles were obtained; furthermore, no differences in size and morphology were detected between unloaded and Mn-loaded vesicles. The encapsulation efficiency of MC and MH was evaluated on extruded liposomes by means of ICP-OES analysis. The obtained results showed that both MC and MH are almost completely retained by the lipid portion of liposomes (LPs), with encapsulation efficiencies of 99.7% for MC and 98.8% for MH. The magnetic imaging properties of the produced liposomal formulations were investigated for application in a potential preclinical scenario by collecting magnetic resonance images of a phantom designed to compare the paramagnetic contrast properties of free MC and MH compounds and the corresponding manganese-containing liposome dispersions. It was found that both LP-MC and LP-MH at low concentrations (0.5 mM) show better contrast (contrast-to-noise ratios of 194 and 209, respectively) than solutions containing free Mn at the same concentrations (117 and 134, respectively) and are safe to use on human cells at the selected dose. Taken together, the results of this comparative analysis suggest that these liposome-containing Mn compounds might be suitable for diagnostic purposes.
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- 2024
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3. Bilosomes and Biloparticles for the Delivery of Lipophilic Drugs: A Preliminary Study
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Maddalena Sguizzato, Francesca Ferrara, Nada Baraldo, Agnese Bondi, Annunziata Guarino, Markus Drechsler, Giuseppe Valacchi, and Rita Cortesi
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bile acids ,nanovesicles ,nanoparticles ,SLN ,NLC ,drug solubility ,Therapeutics. Pharmacology ,RM1-950 - Abstract
In this study, bile acid-based vesicles and nanoparticles (i.e., bilosomes and biloparticles) are studied to improve the water solubility of lipophilic drugs. Ursodeoxycholic acid, sodium cholate, sodium taurocholate and budesonide were used as bile acids and model drugs, respectively. Bilosomes and biloparticles were prepared following standard protocols with minor changes, after a preformulation study. The obtained systems showed good encapsulation efficiency and dimensional stability. Particularly, for biloparticles, the increase in encapsulation efficiency followed the order ursodeoxycholic acid < sodium cholate < sodium taurocholate. The in vitro release of budesonide from both bilosytems was performed by means of dialysis using either a nylon membrane or a portion of Wistar rat small intestine and two receiving solutions (i.e., simulated gastric and intestinal fluids). Both in gastric and intestinal fluid, budesonide was released from bilosystems more slowly than the reference solution, while biloparticles showed a significant improvement in the passage of budesonide into aqueous solution. Immunofluorescence experiments indicated that ursodeoxycholic acid bilosomes containing budesonide are effective in reducing the inflammatory response induced by glucose oxidase stimuli and counteract ox-inflammatory damage within intestinal cells.
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- 2023
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4. Liposomal and Ethosomal Gels: From Design to Application
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Maddalena Sguizzato and Rita Cortesi
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n/a ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
The use of lipid-based nanosystems for topical administration represents an innovative “green” approach, being composed of materials, defined as GRAS (generally recognized as safe), characterized by low toxicity, biocompatibility, and biodegradability [...]
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- 2023
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5. Lipid-Based Nanosystems for the Topical Application of Ferulic Acid: A Comparative Study
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Maddalena Sguizzato, Francesca Ferrara, Markus Drechsler, Anna Baldisserotto, Leda Montesi, Stefano Manfredini, Giuseppe Valacchi, and Rita Cortesi
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ferulic acid ,antioxidant molecules ,transferosomes ,vesicles ,monoolein aqueous dispersions ,topical application ,Pharmacy and materia medica ,RS1-441 - Abstract
In this study, we examined and compared two different lipid-based nanosystems (LBNs), namely Transferosomes (TFs) and Monoolein Aqueous Dispersions (MADs), as delivery systems for the topical application of Ferulic Acid (FA), an antioxidant molecule derived from natural sources. Our results, as demonstrated through Franz-cell experiments, indicate that the LBNs produced with poloxamer 188 in their composition create a multilamellar system. This system effectively controls the release of the drug. Nonetheless, we found that the type of non-ionic surfactant can impact the drug release rate. Regarding FA diffusion from the MAD, this showed a lower diffusion rate compared with the TF. In terms of an in vivo application, patch tests revealed that all LBN formulations tested were safe when applied under occlusive conditions for 48 h. Additionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O3 exposure. Analyses suggest that treatment with TFs composed of poloxamer 188 and MAD formulations might protect against structural skin damage (as observed in hematoxylin/eosin staining) and the development of an oxidative environment (as indicated by 4-hyroxinonenal (4HNE) expression levels) induced by O3 exposure. In contrast, formulations without the active ingredient did not offer protection against the detrimental effects of O3 exposure.Inizio modulo.
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- 2023
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6. A spectrofluorometric analysis to evaluate transcutaneous biodistribution of fluorescent nanoparticulate gel formulations
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Enrica Cappellozza, Federico Boschi, Maddalena Sguizzato, Elisabetta Esposito, Rita Cortesi, Manuela Malatesta, and Laura Calderan
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Organ culture ,bioreactor ,transcutaneous biodistribution ,spectrofluorimetric analysis ,Biology (General) ,QH301-705.5 - Abstract
The investigation of the absorption of drug delivery systems, designed for the transport of therapeutic molecules inside the body, could be relatively simplified by the fluorophore association and tracking by means of bio-imaging techniques (i.e., optical in vivo imaging or confocal and multiphoton microscopy). However, when a fluorescence signal comes out from the skin, its specific detection can be problematic. Skin high autofluorescence can hinder the observation of administered exogenous fluorophores conjugated to drug delivery systems, making it more challenging to detect their biodistribution. In the present study, we have developed a method based on the spectrofluorometric analysis of skin samples to discriminate the fluorescent signal coming from administered fluorescent molecules from the background. Moreover, we gave a semi-quantitative evaluation of the signal intensity. Thus, we distinguished two gel formulations loading the fluorophore rhodamine B (called GEL RHO and GEL SLN-RHO). The two formulations of gels, one of which containing solid lipid nanoparticles (GEL RHO-SLN), were administered on skin explants incubated in a bioreactor, and the penetration was evaluated at different time points (2 and 6 hours). Cryostatic sections of skin samples were observed with confocal laser scanning microscopy, and a spectrofluorometric analysis was performed. Significantly higher signal intensity in the samples administered with SLN-RHO GEL, with a preferential accumulation in the hair bulbs, was found. Reaching also the deeper layers of the hair shaft after 6 hours, the solid lipid nanoparticles thickened with polymer represent a suitable drug delivery system for transcutaneous administration.
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- 2022
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7. Niosomes for Topical Application of Antioxidant Molecules: Design and In Vitro Behavior
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Maddalena Sguizzato, Alessia Pepe, Anna Baldisserotto, Riccardo Barbari, Leda Montesi, Markus Drechsler, Paolo Mariani, and Rita Cortesi
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antioxidant molecules ,niosomes ,vesicles ,hydrogels ,topical application ,nanoparticle solution X-ray scattering ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
In the present study, gels based on xanthan gum and poloxamer 407 have been developed and characterized in order to convey natural antioxidant molecules included in niosomes. Specifically, the studies were conducted to evaluate how the vesicular systems affect the release of the active ingredient and which formulation is most suitable for cutaneous application. Niosomes, composed of Span 20 or Tween 20, were produced through the direct hydration method, and therefore, borate buffer or a micellar solution of poloxamer 188 was used as the aqueous phase. The niosomes were firstly characterized in terms of morphology, dimensional and encapsulation stability. Afterwards, gels based on poloxamer 407 or xanthan gum were compared in terms of spreadability and adhesiveness. It was found to have greater spreadability for gels based on poloxamer 407 and 100% adhesiveness for those based on xanthan gum. The in vitro diffusion of drugs studied using Franz cells associated with membranes of mixed cellulose esters showed that the use of a poloxamer micellar hydration phase determined a lower release as well as the use of Span 20. The thickened niosomes ensured controlled diffusion of the antioxidant molecules. Lastly, the in vivo irritation test confirmed the safeness of niosomal gels after cutaneous application.
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- 2023
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8. Lipid nanostructures for antioxidant delivery: a comparative preformulation study
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Elisabetta Esposito, Maddalena Sguizzato, Markus Drechsler, Paolo Mariani, Federica Carducci, Claudio Nastruzzi, Giuseppe Valacchi, and Rita Cortesi
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α-tocopherol ,cryogenic transmission electron microscopy (cryo-TEM) ,dermocosmetics ,HO-1 ,nanostructured lipid carriers (NLCs) ,retinoic acid ,skin pollution ,solid lipid nanoparticles (SLNs) ,Technology ,Chemical technology ,TP1-1185 ,Science ,Physics ,QC1-999 - Abstract
This investigation is a study of new lipid nanoparticles for cutaneous antioxidant delivery. Several molecules, such as α-tocopherol and retinoic acid, have been shown to improve skin condition and even counteract the effects of exogenous stress factors such as smoking on skin aging. This work describes the design and development of lipid nanoparticles containing antioxidant agents (α-tocopherol or retinoic acid) to protect human skin against pollutants. Namely, solid lipid nanoparticles and nanostructured lipid carriers were prepared using different lipids (tristearin, compritol, precirol or suppocire) in the presence or absence of caprylic/capric triglycerides. The formulations were characterized by particle size analysis, cryogenic transmission electron microscopy, small-angle X-ray diffraction, encapsulation efficiency, preliminary stability, in vitro cytotoxicity and protection against cigarette smoke. Nanostructured lipid carriers were found to reduce agglomerate formation and provided better dimensional stability, as compared to solid lipid nanoparticles, suggesting their suitability for antioxidant loading. Based on the preformulation study, tristearin-based nanostructured lipid carriers loaded with α-tocopherol were selected for ex vivo studies since they displayed superior physico-chemical properties as compared to the other nanostructured lipid carriers compositions. Human skin explants were treated with α-tocopherol-loaded nanostructured lipid carriers and then exposed to cigarette smoke, and the protein levels of the stress-induced enzyme heme oxygenase were analyzed in skin homogenates. Interestingly, it was found that pretreatment with the nanoformulation resulted in significantly reduced heme oxygenase upregulation as compared to control samples, suggesting a protective effect provided by the nanoparticles.
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- 2019
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9. Synthetic and Nanotechnological Approaches for a Diagnostic Use of Manganese
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Maddalena Sguizzato, Petra Martini, Lorenza Marvelli, Walter Pula, Markus Drechsler, Martina Capozza, Enzo Terreno, Lucia Del Bianco, Federico Spizzo, Rita Cortesi, and Alessandra Boschi
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lipid-based nanosystems ,liposomes ,manganese ,PET/MRI ,magnetic susceptibility ,Organic chemistry ,QD241-441 - Abstract
The development of multimodal imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) allows the contemporary obtaining of metabolic and morphological information. To fully exploit the complementarity of the two imaging modalities, the design of probes displaying radioactive and magnetic properties at the same time could be very beneficial. In this regard, transition metals offer appealing options, with manganese representing an ideal candidate. As nanosized imaging probes have demonstrated great value for designing advanced diagnostic/theranostic procedures, this work focuses on the potential of liposomal formulations loaded with a new synthesized paramagnetic Mn(II) chelates. Negatively charged liposomes were produced by thin-layer hydration method and extrusion. The obtained formulations were characterized in terms of size, surface charge, efficiency of encapsulation, stability over time, relaxivity, effective magnetic moment, and in vitro antiproliferative effect on human cells by means of the MTT assay. The negatively charged paramagnetic liposomes were monodisperse, with an average hydrodynamic diameter not exceeding 200 nm, and they displayed good stability and no cytotoxicity. As determined by optical emission spectroscopy, manganese complexes are loaded almost completely on liposomes maintaining their paramagnetic properties.
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- 2022
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10. Ethosomes and Transethosomes as Cutaneous Delivery Systems for Quercetin: A Preliminary Study on Melanoma Cells
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Francesca Ferrara, Mascia Benedusi, Maddalena Sguizzato, Rita Cortesi, Anna Baldisserotto, Raissa Buzzi, Giuseppe Valacchi, and Elisabetta Esposito
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quercetin ,ethosome ,transethosome ,in vitro release test ,in vitro permeation test ,Franz cell ,Pharmacy and materia medica ,RS1-441 - Abstract
The present study is aimed to design ethosomes and transethosomes for topical administration of quercetin. To overcome quercetin low bioavailability, scarce solubility and poor permeability that hamper its pharmaceutical use, the drug was loaded in ethosomes and transethosomes based on different concentrations of phosphatidylcholine. Vesicle morphology was studied by cryogenic transmission electron microscopy, while size distribution and quercetin entrapment capacity were evaluated up to 3 months, respectively, by photon correlation spectroscopy and high-performance liquid chromatography. The antioxidant property was studied by photochemiluminescence test. Quercetin release and permeation was investigated in vitro, using Franz cells associated to different membranes. In vitro assays were conducted on human keratinocytes and melanoma cells to study the behavior of quercetin-loaded nano-vesicular forms with respect to cell migration and proliferation. The results evidenced that both phosphatidylcholine concentration and quercetin affected the vesicle size. Quercetin entrapment capacity, antioxidant activity and size stability were controlled using transethosomes produced by the highest amount of phosphatidylcholine. In vitro permeation studies revealed an enhancement of quercetin permeation in the case of transethosomes with respect to ethosomes. Notably, scratch wound and migration assays suggested the potential of quercetin loaded-transethosomes as adjuvant strategy for skin conditions.
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- 2022
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11. Antisense Oligonucleotides Conjugated with Lipophilic Compounds: Synthesis and In Vitro Evaluation of Exon Skipping in Duchenne Muscular Dystrophy
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Elena Marchesi, Rita Cortesi, Lorenzo Preti, Paola Rimessi, Maddalena Sguizzato, Matteo Bovolenta, and Daniela Perrone
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antisense oligonucleotide ,exon skipping ,conjugation ,2′-O-methyl-phosphorothioate (2′-OMe PS) ,bile acid ,ursodeoxycholic acid (UDCA) ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Our groups previously reported that conjugation at 3′-end with ursodeoxycholic acid (UDCA) significantly enhanced in vitro exon skipping properties of ASO 51 oligonucleotide targeting the human DMD exon 51. In this study, we designed a series of lipophilic conjugates of ASO 51, to explore the influence of the lipophilic moiety on exon skipping efficiency. To this end, three bile acids and two fatty acids have been derivatized and/or modified and conjugated to ASO 51 by automatized solid phase synthesis. We measured the melting temperature (Tm) of lipophilic conjugates to evaluate their ability to form a stable duplex with the target RNA. The exon skipping efficiency has been evaluated in myogenic cell lines first in presence of a transfection agent, then in gymnotic conditions on a selection of conjugated ASO 51. In the case of 5′-UDC-ASO 51, we also evaluated the influence of PS content on exon skipping efficiency; we found that it performed better exon skipping with full PS linkages. The more efficient compounds in terms of exon skipping were found to be 5′-UDC- and 5′,3′-bis-UDC-ASO 51.
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- 2022
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12. Manganese in Diagnostics: A Preformulatory Study
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Maddalena Sguizzato, Walter Pula, Anna Bordin, Antonella Pagnoni, Markus Drechsler, Lorenza Marvelli, and Rita Cortesi
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manganese ,anionic liposomes ,PET/MRI ,lipid-based nanosystem ,Pharmacy and materia medica ,RS1-441 - Abstract
This investigation aims to find lipid-based nanosystems to be used as tools to deliver manganese for diagnostic purposes in multimodal imaging techniques. In particular, the study describes the production and characterization of aqueous dispersions of anionic liposomes as delivery systems for two model manganese-based compounds, namely manganese chloride and manganese acetylacetonate. Negatively charged liposomes were obtained using four different anionic surfactants, namely sodium docusate (SD), N-lauroylsarcosine (NLS), Protelan AG8 (PAG) and sodium lauroyl lactylate (SLL). Liposomes were produced by the direct hydration method followed by extrusion and characterized in terms of size, polydispersity, surface charge and stability over time. After extrusion, liposomes are homogeneous and monodispersed with an average diameter not exceeding 200 nm and a negative surface charge as confirmed by ζ potential measurement. Moreover, as indicated by atomic absorption spectroscopy analyses, the loading of manganese-based compounds was almost quantitative. Liposomes containing NLS or SLL were the most stable over time and the presence of manganese-based compounds did not affect their size distribution. Liposomes containing PAG and SD were instable and therefore discarded. The in vitro cytotoxicity of the selected anionic liposomes was evaluated by MTT assay on human keratinocyte. The obtained results highlighted that the toxicity of the formulations is dose dependent.
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- 2022
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13. Lipid-Based Nanosystems as a Tool to Overcome Skin Barrier
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Maddalena Sguizzato, Elisabetta Esposito, and Rita Cortesi
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liposomes ,cubosomes ,monoolein ,transferosomes ,ethosomes ,SLN ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Skin may be affected by many disorders that can be treated by topical applications of drugs on the action site. With the advent of nanotechnologies, new efficient delivery systems have been developed. Particularly, lipid-based nanosystems such as liposomes, ethosomes, transferosomes, solid lipid nanoparticles, nanostructured lipid carriers, cubosomes, and monoolein aqueous dispersions have been proposed for cutaneous application, reaching in some cases the market or clinical trials. This review aims to provide an overview of the different lipid-based nanosystems, focusing on their use for topical application. Particularly, biocompatible nanosystems able to dissolve lipophilic compounds and to control the release of carried drug, possibly reducing side effects, are described. Notably, the rationale to topically administer antioxidant molecules by lipid nanocarriers is described. Indeed, the structural similarity between the nanosystem lipid matrix and the skin lipids allows the achievement of a transdermal effect. Surely, more research is required to better understand the mechanism of interaction between lipid-based nanosystems and skin. However, this attempt to summarize and highlight the possibilities offered by lipid-based nanosystems could help the scientific community to take advantage of the benefits derived from this kind of nanosystem.
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- 2021
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14. Design of Liposomes Carrying HelixComplex Snail Mucus: Preliminary Studies
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Andrea Alogna, Valentina Gentili, Claudio Trapella, Supandeep Singh Hallan, Maddalena Sguizzato, Giovanni Strazzabosco, Mercedes Fernández, Rita Cortesi, Roberta Rizzo, and Daria Bortolotti
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slime mucus ,HelixComplex ,liposomes ,MTT test ,drug delivery ,Organic chemistry ,QD241-441 - Abstract
In recent decades liposomes have been used in different field thanks to their ability to act as a vehicle for a wide range of biomolecules, their great versatility and their easy production. The aim of this study was to evaluate liposomes as a vehicle for the actives present in the HelixComplex (HC) snail mucus for topical delivery. Liposomes composed of a mixture of phosphatidylcholine, cholesterol and octadecylamine were prepared with and without HC (empty liposomes) and their biological efficacy was tested by evaluating cell viability and migration. HC-loaded liposomes (LHC) were stable throughout 60 days of observation, and showed interesting effects on wound healing reconstitution. In particular, we observed that 25 µg/mL LHC were already able to induce a higher cell monolayer reconstitution in comparison to the untreated samples and HC treated samples after only 4 h (28% versus 10% and 7%, p = 0.03 and p= 0.003, respectively). The effect was more evident at 24 h in comparison with the untreated control (54% versus 21.2% and 41.6%, p = 0.006 and p = NS, respectively). These results represent a preliminary, but promising, novelty in the delivery strategy of the actives present in the HelixComplex mucus.
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- 2021
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15. Mangiferin-Loaded Smart Gels for HSV-1 Treatment
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Mariaconcetta Sicurella, Maddalena Sguizzato, Rita Cortesi, Nicolas Huang, Fanny Simelière, Leda Montesi, Peggy Marconi, and Elisabetta Esposito
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phosphatidylcholine ,Pluronic organogel ,in vitro diffusion ,mangiferin ,HSV-1 ,Pharmacy and materia medica ,RS1-441 - Abstract
Infections due to HSV-1 affect many people all over the world. To counteract this pathology, usually characterized by perioral sores or by less frequent serious symptoms including keratitis, synthetic antiviral drugs are employed, such as acyclovir, often resulting in resistant viral strains under long-term use. Many plant-derived compounds, such as mangiferin and quercetin, have demonstrated antiviral potentials. In this study, smart semisolid forms based on phosphatidylcholine and Pluronic were investigated as delivery systems to administer mangiferin on skin and mucosae affected by HSV-1 infection. Particularly, lecithin organogels, Pluronic gel, and Pluronic lecithin organogels were formulated and characterized. After the selection of gel compositions, physical aspects, such as rheological behavior, spreadability, leakage, and adhesion were evaluated, suggesting a scarce suitability of the lecithin organogel for topical administration. Mangiferin was efficiently included in all type of gels. An in vitro study based on the Franz cell enabled us to find evidence of the gel capability to control drug diffusion, especially in the case of Pluronic organogel, while an in vivo study conducted on human volunteers demonstrated the safeness of all of the gels after cutaneous administration. Furthermore, a plaque reduction assay demonstrated the virucidal effect of mangiferin loaded in a Pluronic gel and a Pluronic lecithin organogel against the HSV-1 KOS strain.
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- 2021
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16. 'Plurethosome' as Vesicular System for Cutaneous Administration of Mangiferin: Formulative Study and 3D Skin Tissue Evaluation
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Maddalena Sguizzato, Francesca Ferrara, Paolo Mariani, Alessia Pepe, Rita Cortesi, Nicolas Huang, Fanny Simelière, Paola Boldrini, Anna Baldisserotto, Giuseppe Valacchi, and Elisabetta Esposito
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phosphatidylcholine ,poloxamer ,mangiferin ,in vitro diffusion ,antioxidant ,Pharmacy and materia medica ,RS1-441 - Abstract
Human skin is dramatically exposed to toxic pollutants such as ozone. To counteract the skin disorders induced by the air pollution, natural antioxidants such as mangiferin could be employed. A formulative study for the development of vesicular systems for mangiferin based on phosphatidylcholine and the block copolymer pluronic is described. Plurethosomes were designed for mangiferin transdermal administration and compared to ethosome and transethosome. Particularly, the effect of vesicle composition was investigated on size distribution, inner and outer morphology by photon correlation spectroscopy, small angle X-ray diffraction, and transmission electron microscopy. The potential of selected formulations as vehicles for mangiferin was studied, evaluating encapsulation efficiency and in vitro diffusion parameters by Franz cells. The mangiferin antioxidant capacity was verified by the 2,2-diphenyl-1-picrylhydrazyl assay. Vesicle size spanned between 200 and 550 nm, being influenced by phosphatidylcholine concentration and by the presence of polysorbate or pluronic. The vesicle supramolecular structure was multilamellar in the case of ethosome or plurethosome and unilamellar in the case of transethosome. A linear diffusion of mangiferin in the case of ethosome and transethosomes and a biphasic profile in the case of plurethosomes indicated the capability of multilamellar vesicles to retain the drug more efficaciously than the unilamellar ones. The antioxidant and anti-inflammatory potential effect of mangiferin against pollutants was evaluated on 3D human skin models exposed to O3. The protective effect exerted by plurethosomes and transethosomes suggests their possible application to enhance the cutaneous antioxidant defense status.
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- 2021
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17. Ethosomes and Transethosomes for Mangiferin Transdermal Delivery
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Maddalena Sguizzato, Francesca Ferrara, Supandeep Singh Hallan, Anna Baldisserotto, Markus Drechsler, Manuela Malatesta, Manuela Costanzo, Rita Cortesi, Carmelo Puglia, Giuseppe Valacchi, and Elisabetta Esposito
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ethosomes ,transethosomes ,mangiferin ,franz cell ,antioxidants ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Mangiferin is a natural glucosyl xanthone with antioxidant and anti-inflammatory activity, making it suitable for protection against cutaneous diseases. In this study ethosomes and transethosomes were designed as topical delivery systems for mangiferin. A preformulation study was conducted using different surfactants in association with phosphatidylcholine. Vesicle dimensional distribution was monitored by photon correlation spectroscopy, while antioxidant capacity and cytotoxicity were respectively assessed by free radical scavenging analysis and MTT on HaCaT keratinocytes. Selected nanosystems were further investigated by cryogenic transmission electron microscopy, while mangiferin entrapment capacity was evaluated by ultracentrifugation and HPLC. The diffusion kinetics of mangiferin from ethosomes and transethosomes evaluated by Franz cell was faster in the case of transethosomes. The suitability of mangiferin-containing nanovesicles in the treatment of skin disorders related to pollutants was investigated, evaluating, in vitro, the antioxidant and anti-inflammatory effect of ethosomes and transethosomes on human keratinocytes exposed to cigarette smoke as an oxidative and inflammatory challenger. The ability to induce an antioxidant response (HO-1) and anti-inflammatory status (IL-6 and NF-kB) was determined by RT-PCR and immunofluorescence. The data demonstrated the effectiveness of mangiferin loaded in nanosystems to protect cells from damage. Finally, to gain insight into the keratinocytes’ uptake of ethosome and transethosome, transmission electron microscopy analyses were conducted, showing that both nanosystems were able to pass intact within the cells.
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- 2021
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18. Data on scaling up and in vivo human study of progesterone lipid nanoparticles
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Elisabetta Esposito, Maddalena Sguizzato, Markus Drechsler, Paolo Mariani, Federica Carducci, Claudio Nastruzzi, and Rita Cortesi
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Science (General) ,Q1-390 - Abstract
Progesterone containing nanoparticles constituted of tristearin or tristearin in association with caprylic-capric triglyceride were produced in a lab scale by ultrasound homogenization and in a pilot scale by high pressure homogenization. A study was conducted to select the pressure to be used in order to obtain homogenously sized nanoparticles. The Dialysis method was performed to mimic subcutaneous administration of lipid nanoparticles. Mathematical analyses of the results were conducted to understand and compare the drug release mechanisms. A human in vivo study, based on tape stripping, was conducted to investigate the performance of nanoparticles as progesterone skin delivery systems. Tape stripped stratum corneum was analyzed by light microscopy.
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- 2017
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19. Challenges in the Physical Characterization of Lipid Nanoparticles
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Supandeep Singh Hallan, Maddalena Sguizzato, Elisabetta Esposito, and Rita Cortesi
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nanoparticles ,solid lipid nanoparticles ,gels ,ethosomes ,liposomes ,nanostructured lipid carriers ,Pharmacy and materia medica ,RS1-441 - Abstract
Nano-sized drug transporters have become an efficient approach with considerable commercial values. Nanomedicine is not only limited to drug delivery by means of different administration routes, such as intravenous, oral, transdermal, nasal, pulmonary, and more, but also has applications in a multitude of areas, such as a vaccine, antibacterial, diagnostics and imaging, and gene delivery. This review will focus on lipid nanosystems with a wide range of applications, taking into consideration their composition, properties, and physical parameters. However, designing suitable protocol for the physical evaluation of nanoparticles is still conflicting. The main obstacle is concerning the sensitivity, reproducibility, and reliability of the adopted methodology. Some important techniques are compared and discussed in this report. Particularly, a comparison between different techniques involved in (a) the morphologic characterization, such as Cryo-TEM, SEM, and X-ray; (b) the size measurement, such as dynamic light scattering, sedimentation field flow fractionation, and optical microscopy; and (c) surface properties, namely zeta potential measurement, is described. In addition, an amperometric tool in order to investigate antioxidant activity and the response of nanomaterials towards the skin membrane has been presented.
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- 2021
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20. The Potential of Caffeic Acid Lipid Nanoparticulate Systems for Skin Application: In Vitro Assays to Assess Delivery and Antioxidant Effect
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Supandeep Singh Hallan, Maddalena Sguizzato, Markus Drechsler, Paolo Mariani, Leda Montesi, Rita Cortesi, Sebastian Björklund, Tautgirdas Ruzgas, and Elisabetta Esposito
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solid lipid nanoparticles ,caffeic acid ,ethosomes ,Franz cell ,skin ,antioxidative reaction ,Chemistry ,QD1-999 - Abstract
The object of this study is a comparison between solid lipid nanoparticles and ethosomes for caffeic acid delivery through the skin. Caffeic acid is a potent antioxidant molecule whose cutaneous administration is hampered by its low solubility and scarce stability. In order to improve its therapeutic potential, caffeic acid has been encapsulated within solid lipid nanoparticles and ethosomes. The effect of lipid matrix has been evaluated on the morphology and size distribution of solid lipid nanoparticles and ethosomes loaded with caffeic acid. Particularly, morphology has been investigated by cryogenic transmission electron microscopy and small angle X-ray scattering, while mean diameters have been evaluated by photon correlation spectroscopy. The antioxidant power has been evaluated by the 2,2-diphenyl-1-picrylhydrazyl methodology. The influence of the type of nanoparticulate system on caffeic acid diffusion has been evaluated by Franz cells associated to the nylon membrane, while to evaluate caffeic acid permeation through the skin, an amperometric study has been conducted, which was based on a porcine skin-covered oxygen electrode. This apparatus allows measuring the O2 concentration changes in the membrane induced by polyphenols and H2O2 reaction in the skin. The antioxidative reactions in the skin induced by caffeic acid administered by solid lipid nanoparticles or ethosomes have been evaluated. Franz cell results indicated that caffeic acid diffusion from ethosomes was 18-fold slower with respect to solid lipid nanoparticles. The amperometric method evidenced the transdermal delivery effect of ethosome, indicating an intense antioxidant activity of caffeic acid and a very low response in the case of SLN. Finally, an irritation patch test conducted on 20 human volunteers demonstrated that both ethosomes and solid lipid nanoparticles can be safely applied on the skin.
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- 2021
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21. Design of Nanosystems for the Delivery of Quorum Sensing Inhibitors: A Preliminary Study
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Supandeep Singh Hallan, Paolo Marchetti, Daria Bortolotti, Maddalena Sguizzato, Elisabetta Esposito, Paolo Mariani, Claudio Trapella, Roberta Rizzo, and Rita Cortesi
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nanotechnological systems ,liposomes ,QS inhibitors ,drug delivery ,biofilm ,MTT test ,Organic chemistry ,QD241-441 - Abstract
Biofilm production is regulated by the Quorum Sensing system. Nowadays, Quorum Sensing represents an appealing target to design new compounds to increase antibiotics effects and avoid development of antibiotics multiresistance. In this research the use of liposomes to target two novel synthetic biofilm inhibitors is presented, focusing on a preformulation study to select a liposome composition for in vitro test. Five different liposome (LP) formulations, composed of phosphatidyl choline, cholesterol and charged surfactant (2:1:1, molar ratio) have been prepared by direct hydration and extrusion. As charged surfactants dicetyl phosphate didecyldimethylammonium chloride, di isobutyl phenoxy ethyl dimethyl benzyl ammonium chloride and stearylamine (SA) and have been used. Liposome charge, size and morphology were investigated by zeta potential, photon correlation spectroscopy, small angle x-ray spectroscopy and electron microscopy. LP-SA was selected for the loading of biofilm inhibitors and subjected to high performance liquid chromatography for entrapment capacity evaluation. LP-SA loaded inhibitors showed a higher diameter (223.6 nm) as compared to unloaded ones (205.7 nm) and a dose-dependent anti-biofilm effect mainly after 48 h of treatment, while free biofilm inhibitors loose activity. In conclusion, our data supported the use of liposomes as a strategy to enhance biofilm inhibitors effect.
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- 2020
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22. Pharmaceutical films made from the waste material from the preparation of propolis extracts: development and characterization
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Lucas de Alcântara Sica de Toledo, Maíra Isabeli Bavato, Hélen Cássia Rosseto, Rita Cortesi, and Marcos Luciano Bruschi
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Própolis/resíduos ,Própolis/resíduos/desenvolvimento de filmes ,Filmes/resíduo de própolis/propriedades físico-químicas ,Polímeros ,Etilcelulose ,Gelatina. ,Pharmacy and materia medica ,RS1-441 - Abstract
abstract This study investigated the development and characterized the physicochemical properties of films obtained from by-products (BP) from the preparation of propolis extracts. Films were produced in the presence and absence of a polymeric adjuvant (gelatin or ethylcellulose) and propylene glycol by a solvent casting method. Density, surface topography by scanning electron microscopy, mechanical properties (folding endurance, tensile strength and percentage elongation), water vapour permeability (WVP), moisture uptake capacity, thermogravimetry, differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR) were determined. The films were a transparent, light greenish-yellow colour, with a uniform surface, and were flexible and easy to handle. The thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout the film. Mechanical properties were influenced by the film composition; films containing gelatin were more resistant to stress, while those containing ethylcellulose were more flexible. Increasing the adjuvant concentration decreased the elasticity and the rupture resistance, but increased the moisture uptake capacity and WVP of the formulations. BP was thermally stable as were the films. FTIR tests suggested interactions between BP and the adjuvants. This work could contribute to the utilization of BP to prepare films for food and pharmaceutical uses
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- 2015
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23. Design and Characterization of Ethosomes for Transdermal Delivery of Caffeic Acid
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Supandeep Singh Hallan, Maddalena Sguizzato, Paolo Mariani, Rita Cortesi, Nicolas Huang, Fanny Simelière, Nicola Marchetti, Markus Drechsler, Tautgirdas Ruzgas, and Elisabetta Esposito
- Subjects
ethosome ,caffeic acid ,penetration enhancers ,in vitro diffusion ,oxygen electrode ,Pharmacy and materia medica ,RS1-441 - Abstract
The present investigation describes a formulative study aimed at designing ethosomes for caffeic acid transdermal administration. Since caffeic acid is characterized by antioxidant potential but also high instability, its encapsulation appears to be an interesting strategy. Ethosomes were produced by adding water into a phosphatidylcholine ethanol solution under magnetic stirring. Size distribution and morphology of ethosome were investigated by photon correlation spectroscopy, small-angle X-ray spectroscopy, and cryogenic transmission electron microscopy, while the entrapment capacity of caffeic acid was evaluated by high-performance liquid chromatography. Caffeic acid stability in ethosome was compared to the stability of the molecule in water, determined by mass spectrometry. Ethosome dispersion was thickened by poloxamer 407, obtaining an ethosomal gel that was characterized for rheological behavior and deformability. Caffeic acid diffusion kinetics were determined by Franz cells, while its penetration through skin, as well as its antioxidant activity, were evaluated using a porcine skin membrane–covered biosensor based on oxygen electrode. Ethosome mean diameter was ≈200 nm and almost stable within three months. The entrapment of caffeic acid in ethosome dramatically prolonged drug stability with respect to the aqueous solution, being 77% w/w in ethosome after six months, while in water, an almost complete degradation occurred within one month. The addition of poloxamer slightly modified vesicle structure and size, while it decreased the vesicle deformability. Caffeic acid diffusion coefficients from ethosome and ethosome gel were, respectively, 137- and 33-fold lower with respect to the aqueous solution. At last, the caffeic acid permeation and antioxidant power of ethosome were more intense with respect to the simple solution.
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- 2020
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24. Ethosomes for Coenzyme Q10 Cutaneous Administration: From Design to 3D Skin Tissue Evaluation
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Maddalena Sguizzato, Paolo Mariani, Francesco Spinozzi, Mascia Benedusi, Franco Cervellati, Rita Cortesi, Markus Drechsler, Roxane Prieux, Giuseppe Valacchi, and Elisabetta Esposito
- Subjects
ethosome ,ubiquinone ,H2O2 ,penetration enhancers ,dermal administration ,reconstituted human epidermis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Ethosome represents a smart transdermal vehicle suitable for solubilization and cutaneous application of drugs. Coenzyme Q10 is an endogenous antioxidant whose supplementation can counteract many cutaneous disorders and pathologies. In this respect, the present study describes the production, characterization, and cutaneous protection of phosphatidylcholine based ethosomes as percutaneous delivery systems for coenzyme Q10. CoQ10 entrapment capacity in ethosomes was almost 100%, vesicles showed the typical ‘fingerprint’ structure, while mean diameters were around 270 nm, undergoing an 8% increase after 3 months from production. An ex-vivo study, conducted by transmission electron microscopy, could detect the uptake of ethosomes in human skin fibroblasts and the passage of the vesicles through 3D reconstituted human epidermis. Immunofluorescence analyses were carried on both on fibroblasts and 3D reconstituted human epidermis treated with ethosomes in the presence of H2O2 as oxidative stress challenger, evaluating 4-hydroxynonenal protein adducts which is as a reliable biomarker for oxidative damage. Notably, the pretreatment with CoQ10 loaded in ethosomes exerted a consistent protective effect against oxidative stress, in both models, fibroblasts and in reconstituted human epidermis respectively.
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- 2020
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25. Nanoparticulate Gels for Cutaneous Administration of Caffeic Acid
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Maddalena Sguizzato, Paolo Mariani, Francesca Ferrara, Markus Drechsler, Supandeep Singh Hallan, Nicolas Huang, Fanny Simelière, Nikul Khunti, Rita Cortesi, Nicola Marchetti, Giuseppe Valacchi, and Elisabetta Esposito
- Subjects
solid lipid nanoparticles ,caffeic acid ,poloxamer ,small angle X-ray scattering ,cigarette smoke ,Chemistry ,QD1-999 - Abstract
Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been loaded in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency and 200 nm mean dimension, as assessed by photon correlation spectroscopy. With the aim to improve the consistence of the aqueous nanodispersions, different types of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized by X-ray and rheological analyses. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was eight-fold slower with respect to the aqueous solution. In addition, the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective role exerted by the nanoparticles.
- Published
- 2020
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26. Ellagic Acid Containing Nanostructured Lipid Carriers for Topical Application: A Preliminary Study
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Supandeep Singh Hallan, Maddalena Sguizzato, Gabriella Pavoni, Anna Baldisserotto, Markus Drechsler, Paolo Mariani, Elisabetta Esposito, and Rita Cortesi
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nanostructured lipid carriers (nlcs) ,lipid-based nanosystems ,phytopharmaceutics ,ellagic acid ,antioxidant activity ,Organic chemistry ,QD241-441 - Abstract
Ellagic acid (EA) is a potent antioxidant substance of natural origin characterized by poor biopharmaceutical properties and low solubility in water that limit its use. The aim of the present study was to develop lipid-based nanoparticle formulations able to encapsulate EA for dermal delivery. The EA-loaded nanoparticles were prepared using two different lipid compositions, namely tristearin/tricaprylin (NLC-EA1) and tristearin/labrasol (NLC-EA2). The influence of formulations on size, entrapment efficiency, and stability of EA-loaded nanoparticles was investigated. Cryo-TEM and small-angle X-ray scattering (SAXS) analyses showed that no morphological differences are evident among all the types of loaded and unloaded nanostructured lipid carriers (NLCs). The macroscopic aspect of both NLC-EA1 and NLC-EA2 did not change with time. No difference in size was appreciable between empty and drug-containing NLC, thus the nanoparticle diameter was not affected by the presence of EA and in general no variations of the diameters occurred during this time. The entrapment efficiency of both EA-loaded nanoparticles was almost quantitative. In addition, NLC-EA1 maintained EA stability for almost two months, while NLC-EA2 up to 40 days. FRAP (Ferric reducing ability of plasma) assay showed an antioxidant activity around 60% for both the loaded NLC, as compared to the solution. Although both types of NLC are characterized by some toxicity on HaCaT cells, NLC-EA1 are less cytotoxic than NLC-EA2. Taken together these results demonstrated that the inclusion of EA within NLC could improve the water solubility, allowing for a reduction of the dosage. Moreover, both types of NLC-EA maintained a high antioxidant effect and low toxicity.
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- 2020
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27. Nafion®-Containing Solid Lipid Nanoparticles as a Tool for Anticancer Pt Delivery: Preliminary Studies
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Maddalena Sguizzato, Elisabetta Esposito, Marcus Drechsler, Eleonora Gallerani, Riccardo Gavioli, Paolo Mariani, Federica Carducci, Rita Cortesi, and Paola Bergamini
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Chemistry ,QD1-999 - Abstract
Preliminary studies of nanoparticles based on the perfluorosulfonic acid resin Nafion have been carried out with the aim of establishing an ionic connection with the protonable phosphine 1,3,5-triaza-7-phosphaadamantane (PTA), suitable for the coordination of platinum. Nafion-containing nanoparticles (NAF) were produced by homogenization followed by ultrasonication method. After production, NAF were characterized in terms of size, morphology, and in vitro cytotoxicity. The PCS studies showed that the Z-average mean diameter was around 250 nm. Moreover, the polydispersity index showed a monodimensional distribution of nanoparticles. Cryo-TEM analysis showed a uniform and homogenous population of particles, characterized by the presence of both ovoidal and needle-like structures. To evaluate the in vitro cytotoxicity, NAF were tested on human cancer cell lines K562 and A2780. No cytotoxic effect was found on both cell lines. By 13P-NMR measures, it is here proved that the strongly acidic sulfonic groups of Nafion-containing nanoparticles (NAF) can act as protonating agents for PTA. The protonation occurs selectively at nitrogen; hence protonated PTA maintains its ability to coordinate platinum via its phosphorus atom.
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- 2017
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28. Production and Characterization of a Clotrimazole Liposphere Gel for Candidiasis Treatment
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Elisabetta Esposito, Maddalena Sguizzato, Christian Bories, Claudio Nastruzzi, and Rita Cortesi
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clotrimazole ,liposphere ,alkyl lactate ,xanthan gum ,Candida albicans ,mucoadhesion ,Organic chemistry ,QD241-441 - Abstract
This study describes the design and characterization of a liposphere gel containing clotrimazole for the treatment of Candida albicans. Lipospheres were produced by the melt-dispersion technique, using a lipid phase constituted of stearic triglyceride in a mixture with caprylic/capric triglyceride or an alkyl lactate derivative. The latter component was added to improve the action of clotrimazole against candida. The liposphere morphology and dimensional distribution were evaluated by scanning electron microscopy. Clotrimazole release kinetics was investigated by an in vitro dialysis method. An anticandidal activity study was conducted on the lipospheres. To obtain formulations with suitable viscosity for vaginal application, the lipospheres were added to a xanthan gum gel. The rheological properties, spreadability, leakage, and adhesion of the liposphere gel were investigated. Clotrimazole encapsulation was always over 85% w/w. The anticandidal study demonstrated that the encapsulation of clotrimazole in lipospheres increased its activity against Candida albicans, especially in the presence of the alkyl lactate derivative in the liposphere matrix. A dialysis method demonstrated that clotrimazole was slowly released from the liposphere gel and that the alkyl lactate derivative further controlled clotrimazole release. Adhesion and leakage tests indicated a prolonged adhesion of the liposphere gel, suggesting its suitability for vaginal application.
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- 2018
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29. Caffeic acid-loaded lipid nanoparticles as a tool to protect skin against oxidative stress: formulation and evaluation on human skin explants
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Maddalena Sguizzato, Francesca Ferrara, Giuseppe Valacchi, Rita Cortesi, and Elisabetta Esposito
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Physiology (medical) ,Biochemistry - Published
- 2023
30. Lipid-Based Nanosystems to Carry Manganese Derivatives for Diagnostic Purpose
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Maddalena Sguizzato, Walter Pula, Markus Drechsler, Lorenza Marvelli, and Rita Cortesi
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- 2022
31. A Correlative Imaging Study of in vivo and ex vivo Biodistribution of Solid Lipid Nanoparticles
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Barbara Cisterna, Manuela Malatesta, Claudio Nastruzzi, Federico Boschi, Andrea Sbarbati, Laura Calderan, Paolo Bernardi, Enrica Cappellozza, Silvia Mannucci, Rita Cortesi, and Elisabetta Esposito
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Biodistribution ,Biocompatibility ,Chemistry ,Organic Chemistry ,Biophysics ,Pharmaceutical Science ,Bioengineering ,02 engineering and technology ,General Medicine ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,In vitro ,0104 chemical sciences ,Biomaterials ,In vivo ,Drug Discovery ,Solid lipid nanoparticle ,Fluorescence microscope ,Nanocarriers ,0210 nano-technology ,Ex vivo - Abstract
Purpose Solid lipid nanoparticles are largely used in biomedical research and are characterized by high stability and biocompatibility and are also able to improve the stability of various loaded molecules. In vitro studies demonstrated that these nanoparticles are low cytotoxic, while in vivo studies proved their efficiency as nanocarriers for molecules characterized by a low bioavailability. However, to our knowledge, no data on the systemic biodistribution and organ accumulation of solid lipid nanoparticles in itself are presently available. Methods In this view, we investigated the solid lipid nanoparticles biodistribution by a multimodal imaging approach correlating in vivo and ex vivo analyses. We loaded solid lipid nanoparticles with two different fluorophores (cardiogreen and rhodamine) to observe them with an optical imager in the whole organism and in the excised organs, and with fluorescence microscopy in tissue sections. Light and transmission electron microscopy analyses were also performed to evaluate possible structural modification or damage due to nanoparticle administration. Results Solid lipid nanoparticles loaded with the two fluorochromes showed good optic characteristics and stable polydispersity. After in vivo administration, they were clearly detectable in the organism. Four hours after the injection, the fluorescent signal occurred in anatomical districts corresponding to the liver and this was confirmed by the ex vivo acquisitions of excised organs. Brightfield, fluorescence and transmission electron microscopy confirmed solid lipid nanoparticles accumulation in hepatocytes without structural damage. Conclusion Our results support the systemic biocompatibility of solid lipid nanoparticles and demonstrate their detailed biodistribution from the whole organism to organs until the cells.
- Published
- 2020
32. Antioxidant-containing monoolein aqueous dispersions: a preliminary study
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Maddalena Sguizzato, Markus Drechsler, Anna Baldisserotto, Rita Cortesi, and Elisabetta Esposito
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vesicles ,animal structures ,Socio-culturale ,vitamin C ,Pharmaceutical Science ,Water ,Monoolein aqueous dispersion ,vitamin E ,Poloxamer ,Cubosomes ,Antioxidants ,Glycerides ,Cubosomes, Monoolein aqueous dispersion, nanoparticles, vesicles, vitamin C, vitamin E ,nanoparticles ,Particle Size - Abstract
The present study describes a preliminary study on the use of monoolein aqueous dispersions (MADs) as delivery systems for antioxidant molecules, namely, ascorbyl palmitate (AP) and alpha-tocopherol (AT). MAD, produced by emulsifying monoolein (4.5% w/w) in water and poloxamer 407 (0.5% w/w) as emulsifier, was characterized in terms of size, morphology, and antioxidant activity by mean of PCS, cryo-TEM, and (2,2-diphenyl-1-picrylhydrazyl) assay. MAD-AP or MAD-AT gave rise to a bimodal size distribution with mean size around 200 nm. All the preparations stored at 25 °C showed quite stable size at least up to 90 days. Cryo-TEM images confirmed MAD size distribution and indicated different MAD morphologies as a function of the loaded antioxidant molecule. Indeed, in the case of MAD-AP, vesicles and cubosomes with the typical inner cubic structure were observed, while vesicles and hexosomes were shown for MAD-AT. The encapsulation efficiency of both antioxidants reached more than 90% with respect to the total amount of drug used for MAD preparation. Moreover, AP and AT antioxidant activity was retained after encapsulation, and in vitro Franz cell experiments showed that the MAD enabled to better control the drug release. These preliminary results suggest that MAD formulations could be further investigated as a potential delivery system for antioxidant supplementation in dietary or cosmetic fields. Graphical abstract
- Published
- 2022
33. Spectrofluorometric analysis to evaluate transcutaneous biodistribution of fluorescent nanoparticulate gel formulations
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Enrica Cappellozza, Federico Boschi, Maddalena Sguizzato, Elisabetta Esposito, Rita Cortesi, Manuela Malatesta, and Laura Calderan
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Drug Carriers ,spectrofluorimetric analysis ,Histology ,integumentary system ,QH301-705.5 ,Biophysics ,Socio-culturale ,Cell Biology ,organ culture, bioreactor, transcutaneous biodistribution, spectrofluorimetric analysis ,organ culture ,bioreactor ,Economica ,Liposomes ,Nanoparticles ,Tissue Distribution ,Particle Size ,Biology (General) ,transcutaneous biodistribution ,Gels ,Skin - Abstract
The investigation of the absorption of drug delivery systems, designed for the transport of therapeutic molecules inside the body, could be relatively simplified by the fluorophore association and tracking by means of bio-imaging techniques (i.e., optical in vivo imaging or confocal and multiphoton microscopy). However, when a fluorescence signal comes out from the skin, its specific detection can be problematic. Skin high autofluorescence can hinder the observation of administered exogenous fluorophores conjugated to drug delivery systems, making it more challenging to detect their biodistribution. In the present study, we have developed a method based on the spectrofluorometric analysis of skin samples to discriminate the fluorescent signal coming from administered fluorescent molecules from the background. Moreover, we gave a semi-quantitative evaluation of the signal intensity. Thus, we distinguished two gel formulations loading the fluorophore rhodamine B (called GEL RHO and GEL SLN-RHO). The two formulations of gels, one of which containing solid lipid nanoparticles (GEL RHO-SLN), were administered on skin explants incubated in a bioreactor, and the penetration was evaluated at different time points (2 and 6 hours). Cryostatic sections of skin samples were observed with confocal laser scanning microscopy, and a spectrofluorometric analysis was performed. Significantly higher signal intensity in the samples administered with SLN-RHO GEL, with a preferential accumulation in the hair bulbs, was found. Reaching also the deeper layers of the hair shaft after 6 hours, the solid lipid nanoparticles thickened with polymer represent a suitable drug delivery system for transcutaneous administration.
- Published
- 2022
34. Manganese in Diagnostics: A Preformulatory Study
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Maddalena Sguizzato, Walter Pula, Anna Bordin, Antonella Pagnoni, Markus Drechsler, Lorenza Marvelli, and Rita Cortesi
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lipid-based nanosystem ,Pharmaceutical Science ,Socio-culturale ,manganese ,anionic liposomes ,PET/MRI ,Article ,RS1-441 ,Economica ,Pharmacy and materia medica ,manganese, anionic liposomes, PET/MRI, lipid-based nanosystem ,LS7_1 ,LS7_7 - Abstract
This investigation aims to find lipid-based nanosystems to be used as tools to deliver manganese for diagnostic purposes in multimodal imaging techniques. In particular, the study describes the production and characterization of aqueous dispersions of anionic liposomes as delivery systems for two model manganese-based compounds, namely manganese chloride and manganese acetylacetonate. Negatively charged liposomes were obtained using four different anionic surfactants, namely sodium docusate (SD), N-lauroylsarcosine (NLS), Protelan AG8 (PAG) and sodium lauroyl lactylate (SLL). Liposomes were produced by the direct hydration method followed by extrusion and characterized in terms of size, polydispersity, surface charge and stability over time. After extrusion, liposomes are homogeneous and monodispersed with an average diameter not exceeding 200 nm and a negative surface charge as confirmed by ζ potential measurement. Moreover, as indicated by atomic absorption spectroscopy analyses, the loading of manganese-based compounds was almost quantitative. Liposomes containing NLS or SLL were the most stable over time and the presence of manganese-based compounds did not affect their size distribution. Liposomes containing PAG and SD were instable and therefore discarded. The in vitro cytotoxicity of the selected anionic liposomes was evaluated by MTT assay on human keratinocyte. The obtained results highlighted that the toxicity of the formulations is dose dependent.
- Published
- 2021
35. Design of Liposomes Carrying HelixComplex Snail Mucus: Preliminary Studies
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Giovanni Strazzabosco, Maddalena Sguizzato, Supandeep Singh Hallan, Roberta Rizzo, Valentina Gentili, M. Fernandez, Andrea Alogna, Daria Bortolotti, Claudio Trapella, and Rita Cortesi
- Subjects
0301 basic medicine ,liposomes ,Spectrophotometry, Infrared ,Snails ,Cell ,HelixComplex ,Pharmaceutical Science ,MTT test ,Article ,Cell Line ,NO ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,QD241-441 ,0302 clinical medicine ,Phosphatidylcholine ,Drug Discovery ,medicine ,Animals ,Freeze Fracturing ,Humans ,LS7_3 ,Viability assay ,Physical and Theoretical Chemistry ,slime mucus ,Wound Healing ,Liposome ,Chromatography ,Cell Death ,Cholesterol ,Organic Chemistry ,drug delivery ,Fibroblasts ,Lipids ,Mucus ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Drug delivery ,Molecular Medicine ,Wound healing - Abstract
In recent decades liposomes have been used in different field thanks to their ability to act as a vehicle for a wide range of biomolecules, their great versatility and their easy production. The aim of this study was to evaluate liposomes as a vehicle for the actives present in the HelixComplex (HC) snail mucus for topical delivery. Liposomes composed of a mixture of phosphatidylcholine, cholesterol and octadecylamine were prepared with and without HC (empty liposomes) and their biological efficacy was tested by evaluating cell viability and migration. HC-loaded liposomes (LHC) were stable throughout 60 days of observation, and showed interesting effects on wound healing reconstitution. In particular, we observed that 25 µg/mL LHC were already able to induce a higher cell monolayer reconstitution in comparison to the untreated samples and HC treated samples after only 4 h (28% versus 10% and 7%, p = 0.03 and p= 0.003, respectively). The effect was more evident at 24 h in comparison with the untreated control (54% versus 21.2% and 41.6%, p = 0.006 and p = NS, respectively). These results represent a preliminary, but promising, novelty in the delivery strategy of the actives present in the HelixComplex mucus.
- Published
- 2021
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36. 'Plurethosome' as Vesicular System for Cutaneous Administration of Mangiferin: Formulative Study and 3D Skin Tissue Evaluation
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Paolo Mariani, Anna Baldisserotto, Paola Boldrini, Francesca Ferrara, Giuseppe Valacchi, Maddalena Sguizzato, Rita Cortesi, Nicolas Huang, Fanny Simelière, Elisabetta Esposito, and Alessia Pepe
- Subjects
Antioxidant ,antioxidant ,medicine.medical_treatment ,Socio-culturale ,Pharmaceutical Science ,Human skin ,02 engineering and technology ,In vitro diffusion ,Mangiferin ,Phosphatidylcholine ,Poloxamer ,Article ,mangiferin ,03 medical and health sciences ,chemistry.chemical_compound ,Pharmacy and materia medica ,medicine ,LS7_3 ,phosphatidylcholine ,030304 developmental biology ,Transdermal ,Polysorbate ,0303 health sciences ,Chemistry ,Vesicle ,Ambientale ,021001 nanoscience & nanotechnology ,in vitro diffusion ,RS1-441 ,Biophysics ,0210 nano-technology ,poloxamer - Abstract
Human skin is dramatically exposed to toxic pollutants such as ozone. To counteract the skin disorders induced by the air pollution, natural antioxidants such as mangiferin could be employed. A formulative study for the development of vesicular systems for mangiferin based on phosphatidylcholine and the block copolymer pluronic is described. Plurethosomes were designed for mangiferin transdermal administration and compared to ethosome and transethosome. Particularly, the effect of vesicle composition was investigated on size distribution, inner and outer morphology by photon correlation spectroscopy, small angle X-ray diffraction, and transmission electron microscopy. The potential of selected formulations as vehicles for mangiferin was studied, evaluating encapsulation efficiency and in vitro diffusion parameters by Franz cells. The mangiferin antioxidant capacity was verified by the 2,2-diphenyl-1-picrylhydrazyl assay. Vesicle size spanned between 200 and 550 nm, being influenced by phosphatidylcholine concentration and by the presence of polysorbate or pluronic. The vesicle supramolecular structure was multilamellar in the case of ethosome or plurethosome and unilamellar in the case of transethosome. A linear diffusion of mangiferin in the case of ethosome and transethosomes and a biphasic profile in the case of plurethosomes indicated the capability of multilamellar vesicles to retain the drug more efficaciously than the unilamellar ones. The antioxidant and anti-inflammatory potential effect of mangiferin against pollutants was evaluated on 3D human skin models exposed to O3. The protective effect exerted by plurethosomes and transethosomes suggests their possible application to enhance the cutaneous antioxidant defense status.
- Published
- 2021
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37. Ethosomes and Transethosomes for Mangiferin Transdermal Delivery
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Supandeep Singh Hallan, Markus Drechsler, Carmelo Puglia, Anna Baldisserotto, Maddalena Sguizzato, Manuela Malatesta, Manuela Costanzo, Elisabetta Esposito, Rita Cortesi, Francesca Ferrara, and Giuseppe Valacchi
- Subjects
0301 basic medicine ,Antioxidant ,ethosomes, transethosomes, mangiferin, Franz cell, antioxidants ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,RM1-950 ,Biochemistry ,Article ,mangiferin ,NO ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,franz cell ,Phosphatidylcholine ,transethosomes ,Xanthone ,ethosomes ,medicine ,LS7_3 ,Mangiferin ,Cytotoxicity ,Molecular Biology ,Transdermal ,Chromatography ,Chemistry ,Cell Biology ,In vitro ,HaCaT ,030104 developmental biology ,antioxidants ,030220 oncology & carcinogenesis ,Therapeutics. Pharmacology - Abstract
Mangiferin is a natural glucosyl xanthone with antioxidant and anti-inflammatory activity, making it suitable for protection against cutaneous diseases. In this study ethosomes and transethosomes were designed as topical delivery systems for mangiferin. A preformulation study was conducted using different surfactants in association with phosphatidylcholine. Vesicle dimensional distribution was monitored by photon correlation spectroscopy, while antioxidant capacity and cytotoxicity were respectively assessed by free radical scavenging analysis and MTT on HaCaT keratinocytes. Selected nanosystems were further investigated by cryogenic transmission electron microscopy, while mangiferin entrapment capacity was evaluated by ultracentrifugation and HPLC. The diffusion kinetics of mangiferin from ethosomes and transethosomes evaluated by Franz cell was faster in the case of transethosomes. The suitability of mangiferin-containing nanovesicles in the treatment of skin disorders related to pollutants was investigated, evaluating, in vitro, the antioxidant and anti-inflammatory effect of ethosomes and transethosomes on human keratinocytes exposed to cigarette smoke as an oxidative and inflammatory challenger. The ability to induce an antioxidant response (HO-1) and anti-inflammatory status (IL-6 and NF-kB) was determined by RT-PCR and immunofluorescence. The data demonstrated the effectiveness of mangiferin loaded in nanosystems to protect cells from damage. Finally, to gain insight into the keratinocytes’ uptake of ethosome and transethosome, transmission electron microscopy analyses were conducted, showing that both nanosystems were able to pass intact within the cells.
- Published
- 2021
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38. Lipid nanostructures for antioxidant delivery: A comparative preformulation study
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Maddalena Sguizzato, Federica Carducci, Paolo Mariani, Elisabetta Esposito, Giuseppe Valacchi, Rita Cortesi, Markus Drechsler, and Claudio Nastruzzi
- Subjects
Antioxidant ,Cryogenic transmission electron microscopy (cryo-TEM), Dermocosmetics, HO-1, Nanostructured lipid carriers (NLCs), Retinoic acid, Skin pollution, Solid lipid nanoparticles (SLNs), α-tocopherol ,Skin pollution ,medicine.medical_treatment ,HO-1 ,Retinoic acid ,Socio-culturale ,General Physics and Astronomy ,Nanoparticle ,Human skin ,02 engineering and technology ,lcsh:Chemical technology ,lcsh:Technology ,Full Research Paper ,03 medical and health sciences ,chemistry.chemical_compound ,Dermocosmetics ,Solid lipid nanoparticle ,medicine ,Nanotechnology ,lcsh:TP1-1185 ,General Materials Science ,Electrical and Electronic Engineering ,lcsh:Science ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,α-tocopherol ,lcsh:T ,021001 nanoscience & nanotechnology ,lcsh:QC1-999 ,Heme oxygenase ,Nanoscience ,Solid lipid nanoparticles (SLNs) ,Cryogenic transmission electron microscopy (cryo-TEM) ,Enzyme ,chemistry ,Nanostructured lipid carriers (NLCs) ,Biophysics ,lcsh:Q ,lipids (amino acids, peptides, and proteins) ,0210 nano-technology ,lcsh:Physics ,Ex vivo - Abstract
This investigation is a study of new lipid nanoparticles for cutaneous antioxidant delivery. Several molecules, such as α-tocopherol and retinoic acid, have been shown to improve skin condition and even counteract the effects of exogenous stress factors such as smoking on skin aging. This work describes the design and development of lipid nanoparticles containing antioxidant agents (α-tocopherol or retinoic acid) to protect human skin against pollutants. Namely, solid lipid nanoparticles and nanostructured lipid carriers were prepared using different lipids (tristearin, compritol, precirol or suppocire) in the presence or absence of caprylic/capric triglycerides. The formulations were characterized by particle size analysis, cryogenic transmission electron microscopy, small-angle X-ray diffraction, encapsulation efficiency, preliminary stability, in vitro cytotoxicity and protection against cigarette smoke. Nanostructured lipid carriers were found to reduce agglomerate formation and provided better dimensional stability, as compared to solid lipid nanoparticles, suggesting their suitability for antioxidant loading. Based on the preformulation study, tristearin-based nanostructured lipid carriers loaded with α-tocopherol were selected for ex vivo studies since they displayed superior physico-chemical properties as compared to the other nanostructured lipid carriers compositions. Human skin explants were treated with α-tocopherol-loaded nanostructured lipid carriers and then exposed to cigarette smoke, and the protein levels of the stress-induced enzyme heme oxygenase were analyzed in skin homogenates. Interestingly, it was found that pretreatment with the nanoformulation resulted in significantly reduced heme oxygenase upregulation as compared to control samples, suggesting a protective effect provided by the nanoparticles.
- Published
- 2019
39. Monoolein liquid crystalline phases for topical delivery of crocetin
- Author
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Nicolas Huang, Fanny Simelière, Paolo Mariani, Giuseppe Romeo, Federica Carducci, Elisabetta Esposito, Carmelo Puglia, and Rita Cortesi
- Subjects
0301 basic medicine ,Stripping (chemistry) ,Surface Properties ,Skin Absorption ,Crocetin,Diffusion,Monoolein,Polarized light microscopy,Small angle x-ray scattering,Tape-Stripping ,Diffusion ,Crocetin ,Socio-culturale ,02 engineering and technology ,Tape-Stripping ,Administration, Cutaneous ,Glycerides ,Monoolein ,03 medical and health sciences ,Viscosity ,chemistry.chemical_compound ,Drug Delivery Systems ,Colloid and Surface Chemistry ,Stratum corneum ,medicine ,Humans ,Lamellar structure ,Particle Size ,Physical and Theoretical Chemistry ,Vitamin A ,Skin ,Transdermal ,Drug Carriers ,Polarized light microscopy ,Crocetin, Monoolein, Polarized light microscopy, Small angle x-ray scattering, Diffusion, Tape-Stripping ,Chemistry ,Surfaces and Interfaces ,General Medicine ,021001 nanoscience & nanotechnology ,Carotenoids ,Small angle x-ray scattering ,Liquid Crystals ,030104 developmental biology ,medicine.anatomical_structure ,Chemical engineering ,0210 nano-technology ,Biotechnology - Abstract
The present investigation concerns the production and characterization of monoolein-water systems designed for cutaneous administration of crocetin. The different monoolein crystalline phases forming in the presence of crocetin as a function of added water have been investigated by x-ray and polarized light microscopy. Franz cell was employed to compare in vitro the crocetin diffusion from selected monoolein water systems containing 95, 90 or 75% w/w of monoolein, while to investigate the performance of monoolein-water as transdermal delivery systems, in vivo studies, based on tape stripping were performed. The presence of micellar, lamellar and Q230 phases was found in the case of systems containing monoolein 95, 90 and 75% w/w respectively, with a viscosity almost directly proportional to the amount of added water. The higher the amount of water, the longer the crocetin stability, while its diffusion was slower in the case of more viscous systems. Tape stripping results indicated a more rapid depletion of crocetin on stratum corneum in the case of systems characterized by cubic phases, followed by micellar and lamellar ones. This behaviour could be related to a more rapid drug penetration throughout the deeper skin strata.
- Published
- 2018
40. Mangiferin loaded smart gels for HSV-1 treatment
- Author
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Fanny Simelière, Peggy Marconi, Maddalena Sguizzato, Mariaconcetta Sicurella, Leda Montesi, Nicolas Huang, Rita Cortesi, and Elisabetta Esposito
- Subjects
Drug ,Pluronic organogel ,food.ingredient ,media_common.quotation_subject ,Pharmaceutical Science ,Socio-culturale ,Pharmacology ,Lecithin ,Article ,mangiferin ,chemistry.chemical_compound ,food ,Pharmacy and materia medica ,In vivo ,Phosphatidylcholine ,phosphatidylcholine ,in vitro diffusion ,HSV-1 ,In vitro study ,LS7_3 ,LS7_1 ,Mangiferin ,media_common ,Ambientale ,Poloxamer ,RS1-441 ,chemistry ,Quercetin - Abstract
Infections due to HSV-1 affect many people all over the world. To counteract this pathology, usually characterized by perioral sores or by less frequent serious symptoms including keratitis, synthetic antiviral drugs are employed, such as acyclovir, often resulting in resistant viral strains under long-term use. Many plant-derived compounds, such as mangiferin and quercetin, have demonstrated antiviral potentials. In this study, smart semisolid forms based on phosphatidylcholine and Pluronic were investigated as delivery systems to administer mangiferin on skin and mucosae affected by HSV-1 infection. Particularly, lecithin organogels, Pluronic gel, and Pluronic lecithin organogels were formulated and characterized. After the selection of gel compositions, physical aspects, such as rheological behavior, spreadability, leakage, and adhesion were evaluated, suggesting a scarce suitability of the lecithin organogel for topical administration. Mangiferin was efficiently included in all type of gels. An in vitro study based on the Franz cell enabled us to find evidence of the gel capability to control drug diffusion, especially in the case of Pluronic organogel, while an in vivo study conducted on human volunteers demonstrated the safeness of all of the gels after cutaneous administration. Furthermore, a plaque reduction assay demonstrated the virucidal effect of mangiferin loaded in a Pluronic gel and a Pluronic lecithin organogel against the HSV-1 KOS strain.
- Published
- 2021
41. The Potential of Caffeic Acid Lipid Nanoparticulate Systems for Skin Application : In Vitro Assays to Assess Delivery and Antioxidant Effect
- Author
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Markus Drechsler, Elisabetta Esposito, Sebastian Björklund, Leda Montesi, Supandeep Singh Hallan, Tautgirdas Ruzgas, Rita Cortesi, Maddalena Sguizzato, and Paolo Mariani
- Subjects
Franz cell ,skin ,Antioxidant ,General Chemical Engineering ,medicine.medical_treatment ,02 engineering and technology ,antioxidative reaction ,Article ,NO ,lcsh:Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Pharmaceutical Sciences ,Solid lipid nanoparticle ,ethosomes ,medicine ,Caffeic acid ,General Materials Science ,Solubility ,030304 developmental biology ,Transdermal ,0303 health sciences ,Chromatography ,food and beverages ,Permeation ,021001 nanoscience & nanotechnology ,Farmaceutiska vetenskaper ,solid lipid nanoparticles ,Membrane ,chemistry ,lcsh:QD1-999 ,Polyphenol ,solid lipid nanoparticles, caffeic acid, ethosomes, Franz cell, skin, antioxidative reaction ,0210 nano-technology ,caffeic acid - Abstract
The object of this study is a comparison between solid lipid nanoparticles and ethosomes for caffeic acid delivery through the skin. Caffeic acid is a potent antioxidant molecule whose cutaneous administration is hampered by its low solubility and scarce stability. In order to improve its therapeutic potential, caffeic acid has been encapsulated within solid lipid nanoparticles and ethosomes. The effect of lipid matrix has been evaluated on the morphology and size distribution of solid lipid nanoparticles and ethosomes loaded with caffeic acid. Particularly, morphology has been investigated by cryogenic transmission electron microscopy and small angle X-ray scattering, while mean diameters have been evaluated by photon correlation spectroscopy. The antioxidant power has been evaluated by the 2,2-diphenyl-1-picrylhydrazyl methodology. The influence of the type of nanoparticulate system on caffeic acid diffusion has been evaluated by Franz cells associated to the nylon membrane, while to evaluate caffeic acid permeation through the skin, an amperometric study has been conducted, which was based on a porcine skin-covered oxygen electrode. This apparatus allows measuring the O2 concentration changes in the membrane induced by polyphenols and H2O2 reaction in the skin. The antioxidative reactions in the skin induced by caffeic acid administered by solid lipid nanoparticles or ethosomes have been evaluated. Franz cell results indicated that caffeic acid diffusion from ethosomes was 18-fold slower with respect to solid lipid nanoparticles. The amperometric method evidenced the transdermal delivery effect of ethosome, indicating an intense antioxidant activity of caffeic acid and a very low response in the case of SLN. Finally, an irritation patch test conducted on 20 human volunteers demonstrated that both ethosomes and solid lipid nanoparticles can be safely applied on the skin.
- Published
- 2021
42. Monolein Aqueous Dispersions as a Tool to Increase Flavonoid Solubility: A Preliminary Study
- Author
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Elisabetta Esposito, Markus Drechsler, Supandeep Singh Hallan, Rita Cortesi, and Maddalena Sguizzato
- Subjects
chemistry.chemical_classification ,animal structures ,Chromatography ,Antioxidant ,Aqueous solution ,medicine.medical_treatment ,Flavonoid ,Rutin ,chemistry.chemical_compound ,chemistry ,Lyotropic ,medicine ,Solubility ,Sodium Cholate ,Quercetin - Abstract
Topical application of flavonoids has recently received increased attention, however their use is limited due to a low aqueous solubility and related low in vivo absorption. Monolein emulsified in water leads to aqueous nanostructured dispersions of complex lyotropic liquid crystalline phases able to carry lipophilic molecules. These monoolein aqueous dispersions (MADs) were investigated on two model flavonoids, namely quercetin and rutin. MADs were produced by emulsifying monoolein in water in the presence of sodium cholate. MAD size, morphology and drug content were characterized using PCS, SdFFF, cryo-TEM and UV spectroscopy. In vitro studies on drug release and antioxidant activity were also conducted. MAD size was found around 300 nm. Cryo-TEM showed that sodium cholate content influences the morphological aspect of MAD. Concerning drug content, MAD increased at least 80-fold quercetin solubility, while the same was not found for rutin. Experiments on antioxidant activity demonstrated the two-fold power of quercetin as compared to rutin while in vitro Franz cell experiments showed that MAD are suitable for cutaneous application. In conclusion MAD can be potentially proposed for the delivery of the antioxidant molecule quercetin, whilst many studies have to be performed for finding a way to deliver rutin.
- Published
- 2020
43. Nanoparticulate Gels for Cutaneous Administration of Caffeic Acid
- Author
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Fanny Simelière, Rita Cortesi, Nicolas Huang, Maddalena Sguizzato, Giuseppe Valacchi, Supandeep Singh Hallan, Nikul Khunti, Nicola Marchetti, Elisabetta Esposito, Francesca Ferrara, Markus Drechsler, and Paolo Mariani
- Subjects
Antioxidant ,General Chemical Engineering ,medicine.medical_treatment ,Sonication ,small angle X-ray scattering ,Socio-culturale ,02 engineering and technology ,Article ,lcsh:Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Economica ,Hyaluronic acid ,Solid lipid nanoparticle ,medicine ,Caffeic acid ,LS7_3 ,General Materials Science ,030304 developmental biology ,0303 health sciences ,Aqueous solution ,Chromatography ,Chemistry ,cigarette smoke ,food and beverages ,Poloxamer ,021001 nanoscience & nanotechnology ,solid lipid nanoparticles ,caffeic acid ,poloxamer ,lcsh:QD1-999 ,Poloxamer 407 ,0210 nano-technology ,medicine.drug - Abstract
Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been loaded in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency and 200 nm mean dimension, as assessed by photon correlation spectroscopy. With the aim to improve the consistence of the aqueous nanodispersions, different types of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized by X-ray and rheological analyses. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was eight-fold slower with respect to the aqueous solution. In addition, the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective role exerted by the nanoparticles.
- Published
- 2020
44. Ellagic Acid Containing Nanostructured Lipid Carriers for Topical Application: A Preliminary Study
- Author
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Anna Baldisserotto, Supandeep Singh Hallan, Gabriella Pavoni, Rita Cortesi, Elisabetta Esposito, Maddalena Sguizzato, Markus Drechsler, and Paolo Mariani
- Subjects
Antioxidant ,lipid-based nanosystems ,medicine.medical_treatment ,Socio-culturale ,Pharmaceutical Science ,Nanoparticle ,antioxidant activity ,02 engineering and technology ,030226 pharmacology & pharmacy ,nanostructured lipid carriers (nlcs) ,Article ,Antioxidants ,Cell Line ,Glycerides ,Nanostructured lipid carriers (NLC), lipid-based nanosystems, phytopharmaceutics, ellagic acid, antioxidant activity ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Organic chemistry ,ellagic acid ,Drug Discovery ,medicine ,Humans ,LS7_3 ,phytopharmaceutics ,Physical and Theoretical Chemistry ,Solubility ,Triglycerides ,Drug Carriers ,Aqueous solution ,Chromatography ,Small-angle X-ray scattering ,Nanostructured lipid carriers (NLC) ,Organic Chemistry ,Ambientale ,021001 nanoscience & nanotechnology ,Ferric reducing ability of plasma ,HaCaT ,chemistry ,Chemistry (miscellaneous) ,Delayed-Action Preparations ,Nanoparticles ,Molecular Medicine ,Caprylates ,0210 nano-technology ,Ellagic acid - Abstract
Ellagic acid (EA) is a potent antioxidant substance of natural origin characterized by poor biopharmaceutical properties and low solubility in water that limit its use. The aim of the present study was to develop lipid-based nanoparticle formulations able to encapsulate EA for dermal delivery. The EA-loaded nanoparticles were prepared using two different lipid compositions, namely tristearin/tricaprylin (NLC-EA1) and tristearin/labrasol (NLC-EA2). The influence of formulations on size, entrapment efficiency, and stability of EA-loaded nanoparticles was investigated. Cryo-TEM and small-angle X-ray scattering (SAXS) analyses showed that no morphological differences are evident among all the types of loaded and unloaded nanostructured lipid carriers (NLCs). The macroscopic aspect of both NLC-EA1 and NLC-EA2 did not change with time. No difference in size was appreciable between empty and drug-containing NLC, thus the nanoparticle diameter was not affected by the presence of EA and in general no variations of the diameters occurred during this time. The entrapment efficiency of both EA-loaded nanoparticles was almost quantitative. In addition, NLC-EA1 maintained EA stability for almost two months, while NLC-EA2 up to 40 days. FRAP (Ferric reducing ability of plasma) assay showed an antioxidant activity around 60% for both the loaded NLC, as compared to the solution. Although both types of NLC are characterized by some toxicity on HaCaT cells, NLC-EA1 are less cytotoxic than NLC-EA2. Taken together these results demonstrated that the inclusion of EA within NLC could improve the water solubility, allowing for a reduction of the dosage. Moreover, both types of NLC-EA maintained a high antioxidant effect and low toxicity.
- Published
- 2020
45. Design of Nanosystems for the Delivery of Quorum Sensing Inhibitors : A Preliminary Study
- Author
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Rita Cortesi, Elisabetta Esposito, Supandeep Singh Hallan, Paolo Mariani, Claudio Trapella, Maddalena Sguizzato, Paolo Marchetti, Roberta Rizzo, and Daria Bortolotti
- Subjects
liposomes ,Biomaterialvetenskap ,nanotechnological systems ,Socio-culturale ,Pharmaceutical Science ,MTT test ,02 engineering and technology ,Article ,biofilm ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Delivery Systems ,Pulmonary surfactant ,lcsh:Organic chemistry ,Drug Discovery ,Zeta potential ,LS7_3 ,Physical and Theoretical Chemistry ,030304 developmental biology ,0303 health sciences ,Liposome ,Bacteria ,Chemistry ,Organic Chemistry ,nanotechnological systems, liposomes,QS inhibitors, drug delivery, biofilm, MTT test ,Biofilm ,Quorum Sensing ,Ambientale ,021001 nanoscience & nanotechnology ,Combinatorial chemistry ,Anti-Bacterial Agents ,Quorum sensing ,Chemistry (miscellaneous) ,Biofilms ,Drug Design ,QS inhibitors ,Drug delivery ,drug delivery ,Biomaterials Science ,Nanoparticles ,Molecular Medicine ,Ammonium chloride ,0210 nano-technology ,Didecyldimethylammonium chloride - Abstract
Biofilm production is regulated by the Quorum Sensing system. Nowadays, Quorum Sensing represents an appealing target to design new compounds to increase antibiotics effects and avoid development of antibiotics multiresistance. In this research the use of liposomes to target two novel synthetic biofilm inhibitors is presented, focusing on a preformulation study to select a liposome composition for in vitro test. Five different liposome (LP) formulations, composed of phosphatidyl choline, cholesterol and charged surfactant (2:1:1, molar ratio) have been prepared by direct hydration and extrusion. As charged surfactants dicetyl phosphate didecyldimethylammonium chloride, di isobutyl phenoxy ethyl dimethyl benzyl ammonium chloride and stearylamine (SA) and have been used. Liposome charge, size and morphology were investigated by zeta potential, photon correlation spectroscopy, small angle x-ray spectroscopy and electron microscopy. LP-SA was selected for the loading of biofilm inhibitors and subjected to high performance liquid chromatography for entrapment capacity evaluation. LP-SA loaded inhibitors showed a higher diameter (223.6 nm) as compared to unloaded ones (205.7 nm) and a dose-dependent anti-biofilm effect mainly after 48 h of treatment, while free biofilm inhibitors loose activity. In conclusion, our data supported the use of liposomes as a strategy to enhance biofilm inhibitors effect.
- Published
- 2020
46. Design and characterization of ethosomes for transdermal delivery of caffeic acid
- Author
-
Maddalena Sguizzato, Paolo Mariani, Fanny Simelière, Rita Cortesi, Elisabetta Esposito, Markus Drechsler, Supandeep Singh Hallan, Nicola Marchetti, Tautgirdas Ruzgas, and Nicolas Huang
- Subjects
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) ,lcsh:RS1-441 ,Pharmaceutical Science ,Socio-culturale ,02 engineering and technology ,Article ,lcsh:Pharmacy and materia medica ,03 medical and health sciences ,chemistry.chemical_compound ,Dynamic light scattering ,Phosphatidylcholine ,medicine ,Caffeic acid ,ethosome ,LS7_3 ,LS7_1 ,Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) ,030304 developmental biology ,Transdermal ,0303 health sciences ,Aqueous solution ,Chromatography ,food and beverages ,Ambientale ,Permeation ,Poloxamer ,021001 nanoscience & nanotechnology ,in vitro diffusion ,chemistry ,penetration enhancers ,Poloxamer 407 ,oxygen electrode ,0210 nano-technology ,caffeic acid ,medicine.drug ,ethosome, caffeic acid, penetration enhancers, in vitro diffusion, oxygen electrode - Abstract
The present investigation describes a formulative study aimed at designing ethosomes for caffeic acid transdermal administration. Since caffeic acid is characterized by antioxidant potential but also high instability, its encapsulation appears to be an interesting strategy. Ethosomes were produced by adding water into a phosphatidylcholine ethanol solution under magnetic stirring. Size distribution and morphology of ethosome were investigated by photon correlation spectroscopy, small-angle X-ray spectroscopy, and cryogenic transmission electron microscopy, while the entrapment capacity of caffeic acid was evaluated by high-performance liquid chromatography. Caffeic acid stability in ethosome was compared to the stability of the molecule in water, determined by mass spectrometry. Ethosome dispersion was thickened by poloxamer 407, obtaining an ethosomal gel that was characterized for rheological behavior and deformability. Caffeic acid diffusion kinetics were determined by Franz cells, while its penetration through skin, as well as its antioxidant activity, were evaluated using a porcine skin membrane&ndash, covered biosensor based on oxygen electrode. Ethosome mean diameter was &asymp, 200 nm and almost stable within three months. The entrapment of caffeic acid in ethosome dramatically prolonged drug stability with respect to the aqueous solution, being 77% w/w in ethosome after six months, while in water, an almost complete degradation occurred within one month. The addition of poloxamer slightly modified vesicle structure and size, while it decreased the vesicle deformability. Caffeic acid diffusion coefficients from ethosome and ethosome gel were, respectively, 137- and 33-fold lower with respect to the aqueous solution. At last, the caffeic acid permeation and antioxidant power of ethosome were more intense with respect to the simple solution.
- Published
- 2020
47. Thermal Magnetic Field Activated Propolis Release From Liquid Crystalline System Based on Magnetic Nanoparticles
- Author
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Patrícia de Souza Bonfim-Mendonça, Federico Spizzo, Lucas de Alcântara Sica de Toledo, Elisabetta Esposito, Elza Kimura, Rita Cortesi, Hélen Cássia Rosseto, Terezinha Inez Estivalet Svidzinski, Marcos Luciano Bruschi, Rafaela Said dos Santos, Lucia Del Bianco, and Maiara Camotti Montanha
- Subjects
magnetic nanoparticles ,Antifungal Agents ,natural products ,Dispersity ,periodontal disease ,Iron oxide ,Socio-culturale ,Pharmaceutical Science ,02 engineering and technology ,Aquatic Science ,Propolis ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Delivery Systems ,0302 clinical medicine ,X-Ray Diffraction ,buccal ,Drug Discovery ,Animals ,Magnetite Nanoparticles ,Cytotoxicity ,Isopropyl myristate ,Ecology, Evolution, Behavior and Systematics ,Ecology ,Rheometry ,Temperature ,030206 dentistry ,General Medicine ,Fibroblasts ,021001 nanoscience & nanotechnology ,Liquid Crystals ,Drug Liberation ,Magnetic Fields ,chemistry ,drug delivery ,Drug delivery ,Magnetic nanoparticles ,magnetic nanoparticles,drug delivery, buccal, natural products, periodontal disease ,Artemia ,0210 nano-technology ,Agronomy and Crop Science ,Nuclear chemistry - Abstract
Intra-periodontal pocket drug delivery systems, such as liquid crystalline systems, are widely utilized improving the drug release control and the therapy. Propolis is used in the treatment of periodontal diseases, reducing the inflammatory and infectious conditions. Iron oxide magnetic nanoparticles (MNPs) can improve the treatment when an alternating external magnetic field (AEMF) is applied, increasing the local temperature. The aim of this study was to develop a liquid crystalline system containing MNPs for intra-periodontal pocket propolis release. MNPs were prepared using iron salts and the morphological, size, thermal, x-ray diffraction, magnetometry, and Mössbauer spectroscopy analyses were performed. Cytotoxicity studies using Artemia salina and fibroblasts were also accomplished. The systems were prepared using polyoxyethylene (10) oleyl ether, isopropyl myristate, purified water, and characterized by polarized optical microscopy, rheometry, and in vitro drug release profile using a periodontal pocket simulator apparatus. The antifungal activity of the systems was investigated against Candida spp. using an AEMF. MNPs displayed nanometric size, were monodisperse, and they displayed very low cytotoxicity. Microscopically homogeneous formulations were obtained displaying important physicochemical and biological properties. The system displayed prolonged release of propolis and important in vitro fungicide activity, which was increased when the AEMF was applied, indicating a potentially alternative therapy for the treatment of the periodontal disease.
- Published
- 2018
48. Solid lipid nanoparticles for the delivery of 1,3,5-triaza-7-phosphaadamantane (PTA) platinum (II) carboxylates
- Author
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Lorenza Marvelli, Federica Carducci, Paola Bergamini, Maddalena Sguizzato, Eleonora Gallerani, Elisabetta Esposito, Paolo Mariani, Markus Drechsler, Rita Cortesi, and Riccardo Gavioli
- Subjects
Magnetic Resonance Spectroscopy ,Materials science ,Stereochemistry ,Dispersity ,Carboxylic Acids ,Socio-culturale ,SLN ,chemistry.chemical_element ,Adamantane ,Antineoplastic Agents ,Bioengineering ,010402 general chemistry ,01 natural sciences ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,Organophosphorus Compounds ,0302 clinical medicine ,Coordination Complexes ,Cell Line, Tumor ,Solid lipid nanoparticle ,Humans ,Particle Size ,PTA, Platinum, SLN, Cancer, Delivery system, Protonolysis ,Delivery system ,Cell Proliferation ,Platinum ,Cancer ,Drug Carriers ,Ligand ,Synthon ,Ambientale ,Lipids ,Combinatorial chemistry ,0104 chemical sciences ,PTA ,chemistry ,Mechanics of Materials ,030220 oncology & carcinogenesis ,Nanoparticles ,Emulsions ,Stearic acid ,Protonolysis ,K562 Cells ,Stearic Acids ,Phosphine - Abstract
The use of solid lipid nanoparticles (SLN) is a promising route for the delivery of platinum complexes aimed to anticancer activity. This paper describes the production and characterization of SLN suitable for the loading of Pt complexes containing the biocompatible phosphine 1,3,5-triaza-7-phosphaadamantane (PTA) as neutral ligand. After a screening of several lipidic phases, stearic acid-based SLN were identified as the most appropriate for the purpose. They were produced by emulsion-dilution method and then characterized in terms of dimension, polydispersity, time stability, pH balance and morphological aspect. Stearic acid SLN are designed as a system able to coordinate to platinum, acting as anionic carboxylic ligands, replacing the base carbonate of the Pt synthon [PtCO3(DMSO)2], where also DMSO can subsequently be substituted by phosphinic ligands, namely PTA. SLN functionalised with Pt-PTA were produced and characterized by this synthetic route. The toxicity of plain SLN and the antiproliferative effect of SLN functionalised with Pt-PTA were evaluated on two human cancer cell lines K562 and A2780. The results indicate that SLN can be exploited as a delivery system for Pt complexes with potential anticancer activity.
- Published
- 2017
49. Microparticles containing gallic and ellagic acids for the biological control of bacterial diseases of kiwifruit plants
- Author
-
Angelo Mazzaglia, Rita Cortesi, Giorgio Mariano Balestra, Maddalena Sguizzato, Antonio Rossetti, Elisabetta Esposito, Massimo Muganu, and Marco Paolocci
- Subjects
0106 biological sciences ,0301 basic medicine ,medicine.drug_class ,030106 microbiology ,Antibiotics ,Biological pest control ,Actinidia spp ,phenolic compounds ,Plant Science ,Horticulture ,Biology ,01 natural sciences ,Microbiology ,Actinidia spp, Pseudomonas syringae pv actinidiae, Pseudomonas syringae pv syringae, Pseudomonas viridiflava, phenolic compounds, sustainable crop protection, spray-drying ,03 medical and health sciences ,chemistry.chemical_compound ,sustainable crop protection ,medicine ,Pseudomonas syringae ,Pseudomonas viridiflava ,spray-drying ,Gallic acid ,Food science ,Pseudomonas syringae pv syringae ,Ambientale ,Plant physiology ,biology.organism_classification ,Antimicrobial ,chemistry ,Pseudomonas syringae pv actinidiae ,Agronomy and Crop Science ,010606 plant biology & botany ,Ellagic acid - Abstract
Over the last decades, kiwifruit cultivation has gained increasing importance all over the world, but some bacterial diseases seriously threaten its cultivation. The most dangerous one is the bacterial canker caused by Pseudomonas syringae pv. actinidiae Takikawa et al., but also floral bud necrosis by Pseudomonas syringae pv. syringae van Hall and bacterial blight by Pseudomonas viridiflava (Burkholder) Dowson affect kiwifruit plants. Their control relies mainly on antibiotics, where allowed, and copper, although this adversely affects the environment, so that alternative control measures are needed. Here we investigate gallic acid and ellagic acid, substances easily obtainable from some plant tissues, for their antimicrobial activity aiming to use them as support in the biocontrol of kiwifruit bacterial diseases. These active principles demonstrated their effectiveness as pure substances in both in vitro and in vivo tests. Moreover, their encapsulation in methacrylate polymeric microparticles showed to improve their usefulness and to prolong remarkably their activity up to 14 days after the treatment, when applied in greenhouse or in field on artificially and naturally infected plants, respectively. The encouraging results obtained by this type of microformulation point the way to future alternative biological control strategies against kiwifruit bacterial diseases.
- Published
- 2017
50. Nanostructured lipid dispersions for topical administration of crocin, a potent antioxidant from saffron (Crocus sativus L.)
- Author
-
Carmelo Puglia, Venera Cardile, Paolo Mariani, Adriana Carol Eleonora Graziano, Elisabetta Esposito, Markus Drechsler, Lucia Crascì, Anna Maria Panico, Rita Cortesi, and Federica Carducci
- Subjects
Antioxidant ,Oxygen radical absorbance capacity ,Administration, Topical ,Glyceride ,medicine.medical_treatment ,ved/biology.organism_classification_rank.species ,Socio-culturale ,Bioengineering ,02 engineering and technology ,Chemical stability ,Formulation ,Materials science ,Nanotechnology ,Antioxidants ,Glycerides ,Biomaterials ,Crocin ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Delivery Systems ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,Crocus sativus ,medicine ,Humans ,Sodium Cholate ,Melanoma ,Antioxidant, Chemical stability, Formulation, Materials science, Nanotechnology ,Chromatography ,ved/biology ,Caseins ,Crocus ,021001 nanoscience & nanotechnology ,Carotenoids ,chemistry ,Mechanics of Materials ,030220 oncology & carcinogenesis ,Drug delivery ,Emulsions ,0210 nano-technology - Abstract
Crocin, a potent antioxidant obtained from saffron, shows anticancer activity in in vivo models. Unfortunately unfavorable physicochemical features compromise its use in topical therapy. The present study describes the preparation and characterization of nanostructured lipid dispersions as drug delivery systems for topical administration of crocin and the evaluation of antioxidant and antiproliferative effects of crocin once encapsulated into nanostructured lipid dispersions. Nanostructured lipid dispersions based on monoolein in mixture with sodium cholate and sodium caseinate have been characterized by cryo-TEM and PCS. Crocin permeation was evaluated in vitro by Franz cells, while the oxygen radical absorbance capacity assay was used to evaluate the antioxidant activity. Furthermore, the antiproliferative activity was tested in vitro by the MTT test using a human melanoma cell line. The emulsification of monoolein with sodium cholate and sodium caseinate led to dispersions of cubosomes, hexasomes, sponge systems and vesicles, depending on the employed emulsifiers. Permeation and shelf life studies demonstrated that nanostructured lipid dispersions enabled to control both rate of crocin diffusion through the skin and crocin degradation. The oxygen radical absorbance capacity assay pointed out an interesting and prolonged antioxidant activity of crocin while the MTT test showed an increase of crocin cytotoxic effect after incorporation in nanostructured lipid dispersions. This work has highlighted that nanostructured lipid dispersions can protect the labile molecule crocin from degradation, control its skin diffusion and prolong antioxidant activity, therefore suggesting the suitability of nanostructured lipid dispersions for crocin topical administration.
- Published
- 2017
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