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Diclofenac is the most prescribed nonsteroidal anti-inflammatory drug worldwide and is used to relieve pain and inflammation in inflammatory arthritis. Diclofenac is associated with serious adverse effects, even in regular-dose regimens. Drug delivery systems can overcome this issue by reducing adverse effects and optimizing their efficacy. This study evaluated the activity of lipid-core nanocapsules loaded with diclofenac (DIC-LNCs) in an experimental model of adjuvant-induced arthritis. The diclofenac nanoformulation was obtained via self-assembly. A stereological analysis approach was applied for the morphological quantification of the volume, density, and cellular profile count of the metatarsophalangeal joints of rats. Proinflammatory cytokines and biochemical profiles were also obtained. Our results showed that the diclofenac nanocapsule DIC-LNCs were able to reduce arthritis compared with the control group and the DIC group. DIC-LNCs efficiently reduced proinflammatory cytokines, C-reactive protein, and xanthine oxidase levels. Additionally, DIC-LNCs reduced the loss of synoviocytes and chondrocytes compared with the DIC (p < 0.05) and control groups (p < 0.05). These data suggest that DIC-LNCs have anti-arthritic activity and preserve joint components, making them promising for clinical use.

Aim: To evaluate the antitumor efficacy of bevacizumab-functionalized nanocapsules in a rat glioblastoma model after the pretreatment with nanocapsules functionalized with a peptide-specific to the epidermal growth factor receptor variant III. Materials & methods: Nanocapsules were prepared, physicochemical characterized and intranasally administered to rats. Parameters such as tumor size, histopathological characteristics and infiltration of CD8+ T lymphocytes were evaluated. Results: The strategy of treatment resulted in a reduction of 87% in the tumor size compared with the control group and a higher infiltration of CD8+ T lymphocytes in tumoral tissue. Conclusion: The block of two different molecular targets using nose-to-brain delivery represents a new and promising approach against glioblastoma.

This study characterized and investigated the toxicity of two multi-walled carbon nanotubes (MWCNT) NM-401 and NM-403 at 60 and 180 µg after four repeated intratracheal instillations; follow-up times were 3, 7, 30 and 90 days after the last instillation. NM-401 was needle-like, long, and thick, while NM-403 was entangled, short and thin. Both MWCNT types induced transient pulmonary and systemic alterations in renal function and oxidative lipid damage markers in recent times. Animals showed general toxicity in the immediate times after exposures, in addition to increased pulmonary LDH release at day 3. In further times, decreased liver and kidney relative weights were noted at higher MWCNT doses. Lung histological damages included pulmonary fibrosis, for both MWCNT types, similarly to asbestos; single liver and kidney histological alterations were present. Repeated instillations led to persistent pulmonary damage at low doses and possibly the extrapulmonary effects may be associated with the consecutive exposures.

Evidence that otoliths, mineral-rich limestone concrescences present in the inner ear of bone fishes, can accelerate bone formation in vivo has been previously reported. The goal of this work was the development, characterization, and evaluation of the cytocompatibility of otoliths-incorporated sodium alginate and gelatin scaffolds. Cynoscion acoupaderived otoliths were characterized by X-ray fluorescence spectrometry (FRX), particle size, free lime, and weight loss by calcination. Furthermore, otoliths were incorporated into sodium alginate (ALG/OTL-s) or gelatin (GEL/OTL-s) scaffolds, previously developed by freeze-drying. Then, the scaffolds were characterized by thermogravimetric analysis (TGA/DTG), differential scanning calorimetry (DSC), infrared spectroscopy with Fourier transform (FTIR), swelling tests, and scanning electron microscopy (SEM). Cytotoxicity assays were run against J774.G8 macrophages and MC3T3-E1 osteoblasts. Data obtained from TGA/DTG, DSC, and FTIR analyses confirmed the interaction between otoliths and the polymeric scaffolds. SEM showed the homogeneous porous 3D structure rich in otolith micro-fragments in both scaffolds. Swelling of the GEL/OTL-s (63.54±3.0%) was greater than of ALG/OTL-s (13.36±9.9%) (p0.05) and significantly higher than that treated with Triton-X (p0.05). However, by 48 h, only ALG/OTL-s showed growth similar to control (p>0.05), whereas GEL/OTL showed a significantly lower growth index (p, We would like to thank the National Council for Scientific and Technological Development (CNPq) and the Foundation for Research and Technological Innovation Support of the State of Sergipe for the financial support in this study. EMBS acknowledges the sponsorship of the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), received support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and was co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

Aim: To develop and characterize bozepinib-loaded lipid-core nanocapsules (BZP-LNC+) as a potential treatment for glioblastoma (GBM). Methods: Characterization of nanocapsules was performed by diameter, polydispersity index, Zeta potential, pH and encapsulation efficiency. GBM cell viability, cell cycle and Annexin/PI were evaluated after BZP-LNC+ treatment. Synergism between BZP-LNC+ and temozolomide (TMZ) was performed by CompuSyn software and confirmed in vitro and in vivo. Results: BZP-LNC+ showed adequate particle sizes, positive Zeta potential, narrow size distribution and high encapsulation efficiency. BZP-LNC+ reduces GBM growth by inducing apoptosis. BZP-LNC+ and TMZ showed synergistic effect in vitro and reduced the in vivo glioma growth by approximately 81%. Conclusion: The present study provides proof-of-principle insights for the combination of these drugs for GBM treatment.

A set of synthetic data, of antibacterial evaluation against gram-positive bacteria, as well as, the interaction of bacterial with lipid-core nanocapsules containing fusidic acid is presented here. In this data set, the analytical data are detailed; serial microdilution; nanoparticle tracking analysis; transmission electron microscopy; minimum inhibitory concentration; diameter size and zeta potential, and infra-red of the formulations before and after contact with bacteria.

Annatto seeds (Bixa orellana L.) are a natural source of norbixin, a carotenoid with antioxidant activity and an intense yellow–orange color which is a commonly used food and beverage colorant. However, it is susceptible to environmental factors such as light, oxygen, and temperature. Microencapsulation presents an alternative for improving the bioactive compound’s stability. In this study, norbixin microcapsules (MCN) were added to isotonic tangerine soft drinks in a quantity not exceeding food additive regulations. The final concentration was 2.86 ± 0.02 µg norbixin/mL, and according to the CIELab system, the beverage acquired the expected orange tonality. The addition of MCN favorably affects beverage stability during storage under accelerated conditions (heat and light), and the half-life time was more significant (29.71 days) than when non-encapsulated norbixin was used (393.39 min). In conclusion, MCN should be considered as an additive with potential use in processed beverage industries instead of synthetic dyes.

Analytical techniques are critical for ensuring physical and chemical stability of a drug both for assessing the stability of drug molecules and for quantifying and identifying the drug content in products. We proposed the development of dry-powders of lipid-core nanocapsules containing dapsone and coated with chitosan, as well as, the analytical quantification of dapsone in dry-powders with 1% and 2% (m/v) of leucine by high-performance liquid chromatography (HPLC). Size is the most relevant physicochemical property of nanoparticulated drug delivery systems. In this context, our results demonstrated that during the powders redispersion in water, could be observed that the mean particle diameters (DAP-LNC-CS-L1 and DAP-LNC-CS-L2) decreased with redispersion times increase. The spray-drying of the lipid-core nanocapsule formulations showed yields ranging from 58 ± 1.0 % (DAP-LNC-CS-L1) to 61 ± 1.5 % (DAP-LNC-CS-L2) indicating an efficient drying process. In this context, the analytical quantifications of dapsone in the dry powders of nanocapsules by HPLC showed that the dapsone content ranged from 92 ± 1.4% (DAP-LNC-CS-L2) to 95 ± 0.8% (DAP-LNC-CS-L1). Can be concluded that spray-drying process of DAP-LNC-CS-L1 and DAP-LNC-CS-L2 formulations showed an efficient aqueous dispersion of nanocapsule powders and the analytical quantification of dapsone in spray-dryed powders were higher than 90%.

Background Resveratrol (RSV) has attracted interest as an alternative drug for the treatment of acute lung injury (ALI) and other pulmonary diseases, but its poor oral bioavailability is a limitation. In this study, we employed drug delivery nanotechnology to improve the stability, lung localization and efficacy of orally administered resveratrol to control lung damage leading to ALI. Methods and materials RSV-loaded lipid-core nanocapsules (RSV-LNCs), prepared by interfacial deposition of biodegradable polymers, were given orally to A/J mice prior to lipopolysaccharide (LPS) intranasal instillation. Inflammatory changes, oxidative stress and lung tissue elastance were assessed 24 h after LPS challenge. Results RSV-LNCs (5 mg/kg), given 1, 4, 6 or 12 h but not 24 h before provocation, inhibited LPS-induced leukocyte accumulation in the bronchoalveolar fluid (BALF), whereas unloaded nanocapsules (ULNCs) or free RSV (5 mg/kg) were ineffective. RSV-LNCs (2.5-10 mg/kg) but not ULNCs or RSV improved lung function and prevented total leukocyte and neutrophil accumulation equally in both BALF and lung tissue when given 4 h before LPS challenge. Similar findings were seen concerning the generation of a range of pro-inflammatory cytokines such as IL-6, KC, MIP-1α, MIP-2, MCP-1 and RANTES in lung tissue. In addition, only RSV-LNCs inhibited MDA levels and SOD activity in parallel with blockade of the ERK and PI3K/Akt pathways following LPS provocation. Conclusion Nanoformulation of RSV in biodegradable oil-core polymers is an effective strategy to improve the anti-ALI activity of RSV, suggesting that the modified-release formulation of this plant polyphenol may be of great value in clinical conditions associated with ALI and respiratory failure.

Aim: Poly(ε-caprolactone) lipid-core nanocapsules (LNCs) are efficient drug carriers and drug-free LNCs display therapeutic effects, inhibiting tumor growth and neutrophil activities. Herein, we investigated the direct actions of LNCs on human immune cells, to guide their therapeutic application. Materials & methods: LNC’s uptake, cytokine release, cell migration, proliferation and intracellular pathways under inflammatory stimulation were investigated. Results & conclusion: LNCs quickly penetrated leukocytes without cytotoxicity; inhibited mitogen-induced lymphocyte proliferation, cytokine release and leukocyte migration under inflammatory stimulation, which were associated with inhibition of the MAP kinase pathway and intracellular calcium influx. Hence, we showed LNCs as a down-regulatory agent on immune cells, suggesting that either the particles themselves or their application as a drug carrier can halt non-desired inflammatory processes.

The data presented here are related to the research paper entitled “Chemical stability, mass loss and hydrolysis mechanism of sterile and non-sterile lipid-core nanocapsules: the influence of the molar mass of the polymer wall,” [1]. Experimental details of the nanoemulsion and nanosphere preparation. Sterilization methodology and their efficacy by microbiological analyses (turbidimetry and fungi and bacteria detection). Characterization data of formulations, LNC 1, LNC 2 and LNC 3, analyzed by laser diffraction and DLS analysis, as well as, characterization data of degradation by SEC, including all statistics analyses.

The use of cactus cladode mucilage (Opuntia monacantha) was exploited as a new natural structuring material to zeaxanthin nanoencapsulation. The zeaxanthin nanoparticles (Zea-NP) were characterized regarding particle size distribution, span value, zeta potential, pH, viscosity, color, morphology, thermal properties, encapsulation efficiency and FTIR spectroscopy after preparation. A nanoemulsion (Zea-NE) was developed and evaluated to compare the physicochemical properties and stability with the nanoencapsulated zeaxanthin. The stability of nanoencapsulated and unencapsulated zeaxanthin was evaluated during 28 days of storage at 4, 25 and 40 °C regarding particle size, span value, pH, color, and zeaxanthin retention (%). Zea-NP presented a mean diameter of 184 ± 3.54 nm and homogeneous distribution, zeta potential of -14.8 ± 0.42 mV and encapsulation efficiency of 96.57%. Zea-NP showed spherical shape, and the thermal analyses indicated that nanoparticles were more stable than nanoemulsion. After 28 days of storage at 25 °C and 40 °C, the zeaxanthin retention in Zea-NP was higher than in Zea-NE. The obtained results support that cactus cladode mucilage protected zeaxanthin from degradation and have potential to be used as structuring material in nanoencapsulation.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inflammatory and oxidative imbalance lung conditions with no successful pharmacological therapy and a high mortality rate. Resveratrol (RSV) is a plant-derived stilbene that presents anti-inflammatory and antioxidant effects. However, its therapeutic application remains limited due to its poor bioavailability, which can be solved by the use of nanocarriers. Previously, we demonstrated that nanoencapsulated RSV (RSV-LNC) pre-treatment, performed 4 h before lipopolysaccharide (LPS) stimulation in mice, increased its anti-inflammatory properties. In this study, we evaluated the anti-inflammatory and antioxidant effects, and lung distribution of RSV-LNCs administered therapeutically (6 h post LPS exposure) in a lung injury mouse model. The results showed that RSV-LNCs posttreatment improved lung function and diminished pulmonary inflammation. Moreover, RSV-LNC treatment enhanced the antioxidant catalase level together with a decrease in the oxidative biomarker in mouse lungs, which was accompanied by an increase in pulmonary Nrf2 antioxidant expression. Finally, the presence of RSV in lung tissue was significantly detected when mice received RSV-LNCs but not when they received RSV in its free form. Together, our results confirm that RSV nanoencapsulation promotes an increase in RSV bioavailability, enhancing its therapeutic effects in an LPS-induced lung injury model.

Glioblastoma (GB) is a histological and genetically heterogeneous brain tumor that is highly proliferative and vascularized. The prognosis is poor with currently available treatment. In this study, we evaluated the cytotoxicity and antiangiogenic activity of doxorubicin-loaded-chitosan-coated-arginylglycylaspartic acid-functionalized-poly(ε-caprolactone)-alpha bisabolol-LNC (AB-DOX-LNC-L-C-RGD). The nanoformulation was prepared by self-assembling followed by interfacial reactions, physicochemically characterized and evaluated in vitro against GB cell lines (U87MG and U138MG) and in vivo using the chicken chorioallantoic membrane assay (CAM). Spherical shape nanocapsules had a hydrodynamic mean diameter of 138 nm, zeta potential of +13.4 mV, doxorubicin encapsulation of 65%, and RGD conjugation of 92%. After 24 h of treatment (U87MG and U138MG), the median inhibition concentrations (IC50) were 520 and 490 nmol L−1 doxorubicin-equivalent concentrations, respectively. The treatment induced antiproliferative activity with S-phase cell-cycle arrest and apoptosis in the GB cells. Furthermore, after 48 h of exposure, evaluation of antiangiogenic activity (CAM) showed that the relative vessel growth following treatment with the nanocapsules was 5.4 times lower than that with the control treatment. The results support the therapeutic potential of the nanoformulation against GB and, thereby, pave the way for future preclinical studies.

Breast cancer is the most common cancers among women and is one of the main causes of morbidity and mortality in this population. In this study, we aimed to conjugate doxorubicin (DOX), a drug widely used in cancer chemotherapy, and folic acid (FA), a ligand targeted for cancer therapy, to lipid-core nanocapsules (LNC), and evaluate the efficacy of the nanoformulation against triple-negative breast cancer (TNBC) MDA-MB-231 cells that overexpress folate receptors (FRs). We performed cell viability assays, quantitative real-time PCR (qRT-PCR), cell migration assay, and clonogenic assay, as well as measured the levels of nitric oxide (NO) generated and cellular uptake. The results showed that the nanoformulation reduced cell viability. The results of qRT-PCR analysis revealed that the nanoformulation induced apoptosis of MDA-MB-231 cells. The mRNA expression levels of Cat and MnSod were increased when the nanoformulation was compared to the doxorubicin solution. Furthermore, the nanoformulation significantly decreased the migration of breast cancer cells in vitro and inhibited colony formation. Additionally, the expression of iNOS in MDA-MB-231 cells was higher when the nanoformulation was used compared to the doxorubicin solution. Cellular uptake was observed after incubating the MDA-MB-231 cells with the fluorescent-labeled nanoformulation. In conclusion, we developed a promising nanoformulation for the treatment of TNBC. Further studies are necessary to demonstrate the in vivo efficacy of this formulation.

Atherosclerosis is a non-resolving inflammatory condition that underlies major cardiovascular diseases. Recent clinical trial using an anti-inflammatory drug has shown a reduction of cardiovascular mortality, but increased the susceptibility to infections. For this reason, tissue target anti-inflammatory therapies can represent a better option to regress atherosclerotic plaques. Docosahexaenoic acid (DHA) is a natural omega 3 fatty acid component of algae oil and acts as a precursor of several anti-inflammatory compounds, such the specialized proresolving lipid mediators (SPMs). During the atherosclerosis process, the inflammatory condition of the endothelium leads to the higher expression of adhesion molecules, such as Endothelial Cell Adhesion Molecule Plate 1 (PECAM-1 or CD31), as part of the innate immune response. Thus, the objective of this study was to develop lipid-core nanocapsules with DHA constituting the nucleus and anti-PECAM-1 on their surface and drive this structure to the inflamed endothelium. Nanocapsules were prepared by interfacial deposition of pre-formed polymer method. Zinc-II was added to bind anti-PECAM-1 to the nanocapsule surface by forming an organometallic complex. Swelling experiment showed that the algae oil act as non-solvent for the polymer (weight constant weight for 60 days, p > 0.428) indicating an adequate material to produce kinetically stable lipid-core nanocapsules (LNC). Five formulations were synthesized: Lipid-core nanocapsules containing DHA (LNC-DHA) or containing Medium-chain triglycerides (LNC-MCT), multi-wall nanocapsules containing DHA (MLNC-DHA) or containing MCT (MLNC-MCT) and the surface-functionalized (anti-PECAM-1) metal-complex multi-wall nanocapsules containing DHA (MCMN-DHA-a1). All formulations showed homogeneous macroscopic aspects without aggregation. The mean size of the nanocapsules measured by laser diffraction did not show difference among the samples (p = 0.241). Multi-wall nanocapsules (MLNC) showed a slight increase in the mean diameter and polydispersity index (PDI) measured by DLS, lower pH and an inversion in the zeta-potential (ξP) compared to LNCs. Conjugation test for anti-PECAM-1 showed 94.80% of efficiency. The mean diameter of the formulation had slightly increased from 160 nm (LCN-DHA) and 162 nm (MLNC-DHA) to 164 nm (MCMN-DHA-a1) indicating that the surface functionalization did not induce aggregation of the nanocapsules. Biological assays showed that the MCMN-DHA-a1 were uptaken by the HUVEC cells and did not decrease their viability. The surface-functionalized (anti- PECAM-1) metal-complex multi-wall nanocapsules containing DHA (MCMN-DHA-a1) can be considered adequate for pharmaceutical approaches.

Pequi is a Brazilian fruit used in folk medicine for pulmonary diseases treatment, but its oil presents bioavailability limitations. The use of nanocarriers can overcome this limitation. We developed nanoemulsions containing pequi oil (pequi-NE) and evaluated their effects in a lipopolysaccharide (LPS)-induced lung injury model. Free pequi oil or pequi-NE (20 mg/kg) was orally administered to A/J mice 16 and 4 h prior to intranasal LPS exposure, and the analyses were performed 24 h after LPS provocation. The physicochemical results revealed that pequi-NE comprised particles with mean diameter of 174&ndash, 223 nm, low polydispersity index (0.11 &plusmn, 0.01), zeta potential of &minus, 7.13 &plusmn, 0.08 mV, and pH of 5.83 &plusmn, 0.12. In vivo evaluation showed that free pequi oil pretreatment reduced the influx of inflammatory cells into bronchoalveolar fluid (BALF), while pequi-NE completely abolished leukocyte accumulation. Moreover, pequi-NE, but not free pequi oil, reduced myeloperoxidase (MPO), TNF-&alpha, IL-1&beta, IL-6, MCP-1, and KC levels. Similar anti-inflammatory effects were observed when LPS-exposed animals were pre-treated with the nanoemulsion containing pequi or oleic acid. These results suggest that the use of nanoemulsions as carriers enhances the anti-inflammatory properties of oleic acid-containing pequi oil. Moreover, pequi&rsquo, s beneficial effect is likely due its high levels of oleic acid.

Objectives: In this study, we investigated the potential of amoxicillin-loaded polymeric microspheres to be delivered to tooth root infection sites via a bioactive reparative cement.Materials and methods: Amoxicillin-loaded microspheres were synthesized by a spray-dray method and incorporated at 2.5% and 5% into a mineral trioxide aggregate cement clinically used to induce a mineralized barrier at the root tip of young permanent teeth with incomplete root development and necrotic pulp. The formulations were modified in liquid:powder ratios and in composition by the microspheres. The optimized formulations were evaluated in vitro for physical and mechanical eligibility. The morphology of microspheres was observed under scanning electron microscopy.Results: The optimized cement formulation containing microspheres at 5% exhibited a delayed-release response and maintained its fundamental functional properties. When mixed with amoxicillin-loaded microspheres, the setting times of both test materials significantly increased. The diametral tensile strength of cement containing microspheres at 5% was similar to control. However, phytic acid had no effect on this outcome (p > 0.05). When mixed with modified liquid:powder ratio, the setting time was significantly longer than that original liquid:powder ratio (p < 0.05).Conclusions: Lack of optimal concentrations of antibiotics at anatomical sites of the dental tissues is a hallmark of recurrent endodontic infections. Therefore, targeting the controlled release of broad-spectrum antibiotics may improve the therapeutic outcomes of current treatments. Overall, these results indicate that the carry of amoxicillin by microspheres could provide an alternative strategy for the local delivery of antibiotics for the management of tooth infections.

This study investigated plasma and brain disposition of quetiapine lipid core nanocapsules (QLNC) in naive and schizophrenic (SCZ-like) rats and developed a semimechanistic model to describe changes in both compartments following administration of the drug in solution (FQ) or nanoencapsulated. QLNC (1 mg/ml) presented 166 ± 39 nm, low polydispersity, and high encapsulation (93.0% ± 1.4%). A model was built using experimental data from total and unbound plasma and unbound brain concentrations obtained by microdialysis after administration of single intravenous bolus dose of FQ or QLNC to naive and SCZ-like rats. A two-compartment model was identifiable both in blood and in brain with a bidirectional drug transport across the blood-brain barrier (CLin and CLout). SCZ-like rats' significant decrease in brain exposure with FQ (decrease in CLin) was reverted by QLNC, showing that nanocarriers govern quetiapine tissue distribution. Model simulations allowed exploring the potential of LNC for brain delivery. SIGNIFICANCE STATEMENT: A population approach was used to simultaneously model total and unbound plasma and unbound brain quetiapine concentrations allowing for quantification of the rate and extent of the drug's brain distribution following administration of both free drug in solution or as nanoformulation to naive and SCZ-like rats. The model-based approach is useful to better understand the possibilities and limitations of this nanoformulation for drug delivering to the brain, opening the opportunity to use this approach to improve SCZ-treatment-limited response rates.

Aim: To characterize a method to isolate glioma-derived extracellular vesicles (GEVs) and understand their role in immune system modulation and glioma progression. Materials & methods: GEVs were isolated by differential centrifugation from C6 cell supernatant and characterized by size and expression of CD9, HSP70, CD39 and CD73. The glioma model was performed by injecting C6 glioma cells into the right striatum of Wistar rats in the following groups: controls (C6 cells alone), coinjection (C6 cells + GEVs) and GEVs by intranasal administration followed by immune cells, tumor size and cells proliferation analyses. Results: GEVs presented uniform size (175 nm), expressed CD9, HSP70, CD39, CD73 and produced adenosine. In vivo, we observed a reduction in tumor size, in cell proliferation (Ki-67) and in a regulatory cell marker (FoxP3). Conclusion: GEVs, administered before or at tumor challenge, have antiproliferative properties and reduce regulatory cells in the glioma microenvironment.

Multi-wall lipid-core nanocapsule (MLNC) functionalized with captopril and nanoencapsulating furosemide within the core was developed as a liquid formulation for oral administration. The nanocapsules had mean particle size below 200 nm, showing unimodal and narrow size distributions with moderate dispersity (laser diffraction and dynamic light scattering). Zeta potential was inverted from &minus, 14.3 mV [LNC-Fur(0,5)] to +18.3 mV after chitosan coating. Transmission electron microscopy and atomic force microscopy showed spherical structures corroborating the nanometric diameter of the nanocapsules. Regarding the systolic pressure, on the first day, the formulations showed antihypertensive effect and a longer effect than the respective drug solutions. When both drugs were associated, the anti-hypertensive effect was prolonged. On the fifth day, a time effect reduction was observed for all treatments, except for the nanocapsule formulation containing both drugs [Capt(0.5)-Zn(25)-MLNC-Fur(0.45)]. For diastolic pressure, only Capt(0.5)-Zn(25)-MLNC-Fur(0.45) presented a significant difference (p &lt, 0.05) on the first day. On the fifth day, both Capt(0.5)-MLNC-Fur(0.45) and Capt(0.5)-Zn(25)-MLNC-Fur(0.45) had an effect lasting up to 24 h. The analysis of early kidney damage marker showed a potential protection in renal function by Capt(0.5)-Zn(25)-MLNC-Fur(0.45). In conclusion, the formulation Capt(0.5)-Zn(25)-MLNC-Fur(0.45) proved to be suitable for hypertension treatment envisaging an important innovation.

A high-performance liquid chromatography-ultraviolet (HPLC-UV) method was developed and validated for simultaneous determination of Resveratrol (RSV) and Lipoic Acid (LA). A C18 column was used with a mobile phase consisting of acetonitrile and 0.01M phosphoric acid (60:40). The detection wavelength was at 235 nm. The method was specific in the presence of pharmaceutical excipients widely used in solid dosage forms or lipid-core nanocapsules. The results demonstrated linearity between 5 and 50 µg/mL for RSV and 30 and 120 µg/mL for LA. The method presented precision and accuracy (RSD

Raloxifene hydrochloride (RH) is a selective oestrogen receptor modulator used for the treatment of osteoporosis. Even though 60% of an oral dose is quickly absorbed via the gastrointestinal tract, the absolute bioavailability of RH is only 2–3% in humans due to extensive first-pass metabolism. Various approaches to improve RH bioavailability have been reported over the past few years; however, none have focused on the development of products for pulmonary administration. Therefore, in this study, submicron particles containing RH were produced for pulmonary administration with the aim to limit first-pass metabolism. Powders were produced by vibrational atomisation spray drying with a high process yield (>80%). The drug content was between 440 and 890 mg·g−1, and powders had a high encapsulation efficiency (>95%), mean particle size of 400–700 nm, low residual moisture ( 55%) and adequate mass median aerodynamic diameter for pulmonary delivery (

Background Melatonin has been described in the literature as a potent antioxidant. However, melatonin presents variable, low bioavailability and a short half-life. The use of polymeric nanoparticulated systems has been proposed for controlled release. Thus, the purpose of this study was to investigate the action of melatonin-loaded lipid-core nanocapsules (Mel-LNC) in the antioxidant system of Caenorhabditis elegans, and the possible protective effect of this formulation against lipid peroxidation caused by paraquat (PQ). Methods The suspensions were prepared by interfacial deposition of the polymer and were physiochemically characterized. C. elegans N2 wild type and transgenic worm CF1553, muls84 [sod-3p::gfp; rol6(su1006)] were obtained from the Caenorhabditis Genetics Center (CGC). The worms were divided into 5 groups: Control, PQ 0.5 mM, PQ 0.5 mM + Mel-LNC 10 μg/mL, PQ + unloaded lipid-core nanocapsules (LNC), and PQ + free melatonin (Mel) 10 μg/mL. The lipid peroxidation was assessed through thiobarbituric acid (TBARS) levels and the fluorescence levels of the transgenic worms expressing GFP were measured. Results The LNC and Mel-LNC presented a bluish-white liquid, with pH values of 5.56 and 5.69, respectively. The zeta potential was − 6.4 ± 0.6 and − 5.2 ± 0.2, respectively. The mean particle diameter was 205 ± 4 nm and 203 ± 3 nm, respectively. The total melatonin content was 0.967 mg/ml. The TBARS levels were significantly higher in the PQ group when compared to the control group (p p C. elegans from lipid peroxidation caused by PQ and this was not observed when free melatonin was used. Moreover, Mel-LNC increased the fluorescence intensity of the transgenic strain that encodes the antioxidant enzyme SOD-3, demonstrating a possible mechanism of protection from PQ-induced damage. Conclusion These findings demonstrated that melatonin, when associated with nanocapsules, had improved antioxidant properties and the protective activity against PQ-induced lipid peroxidation could be associated with the activation of antioxidant enzymes by Mel-LNC in C. elegans.

Natália Rubio Claret Pereira,1,* Rodrigo Azevedo Loiola,1,* Stephen Fernandes Rodrigues,1 Catiuscia P de Oliveira,2 Sabrina L Büttenbender,3 Silvia S Guterres,2 Adriana R Pohlmann,3 Sandra H Farsky1 1Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, Sao Paulo, Brazil; 2Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 3Department of Organic Chemistry, Institute of Chemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil *These authors contributed equally to this work Purpose: The low penetration of drugs across the blood–brain barrier (BBB) compromises the delivery of chemotherapeutic agents to the brain parenchyma and contributes to the poor prognosis of glioblastoma multiforme (GBM). We investigated the efficacy of methotrexate-loaded lipid-core nanocapsules (MTX-LNC) administered by the oral route to treat murine GBM, its ability to cross the BBB, and the mechanisms of MTX-LNC uptake by cultured GL261 glioma and BV2 microglia cells. Materials and methods: Female C57B/6 mice were used in intravital microscopy assays to investigate the penetrance of rhodamine B-label MTX-LNC (RhoB/MTX-LNC) in the brain after oral or IV administration, and to evaluate the BBB integrity. Intracranial implantation of GL261 cells was undertaken to induce a murine GBM model, and the effectiveness of oral MTX or MTX-LNC treatments (started on Day 10 of GBM, every 2 days for 12 days) was quantified by tumor size, body weight, and leukogram. Pharmacological blockade of endocytic pathways was done to investigate the mechanisms of MTX-LNC uptake by cultured GL261 and microglia BV2 cells by using fluorescence microscopy. The effect of MTX-LNC or MTX on GL261 and BV2 proliferation was evaluated to compare the cytotoxicity of such compounds. Results: RhoB/MTX-LNC was detected in brain parenchyma of mice after IV or oral administration, without any damage on BBB. Oral treatment with MTX-LNC reduced tumor volume and prevented weight loss and leukopenia in comparison to MTX-treated mice. MTX-LNC uptake by GL261 is caveolae-dependent, whereas endocytosis of MTX-LNC by BV2 occurs via phagocytosis and macropinocytosis. Both MTX-LNC and MTX reduced GL261 and BV2 proliferation; however, MTX-LNC showed higher efficacy in the inhibition of glioma proliferation. Conclusion: Together, we infer that the higher ability of MTX-LNC to cross the BBB and be captured by cancer and immune brain cells by different mechanisms is responsible for the higher efficacy of oral MTX-LNC treatment in GBM. Keywords: glioma, nanomedicine, blood–brain barrier, microglia, endocytosis

Nanostructured drug delivery systems have been extensively studied, mainly for applications in cancer therapy. The advantages of these materials include protection against drug degradation and improvement in both the relative solubility of poorly water soluble drugs as in targeting of therapy, due to the enhanced permeability and retention effect on tumor sites. In this work, we evaluate the antitumor activity of tretinoin-loaded lipid core nanocapsules (TT-LNC) in a tretinoin-resistant breast cancer cell-line, MDA-MB- 231, as well as the synergistic effect of combination of this treatment with 5-FU or DOXO. The inhibition of cell growth was assayed by MTT reduction. Live/Dead assay and DAPI staining evaluated cytotoxicity. Apoptosis was evaluated by Annexin V-PE/7AAD and the effect of chronic exposure was evaluated by colony formation assay. TT-LNC reduced the cell viability even at lower concentrations (1 μM) and displayed synergistic effect with 5-FU or DOXO on cytotoxicity and colony formation inhibition. Our work shows a possibility of using nanocapsules to improve the antitumoral activity of TT for its use either alone or in combination with other chemotherapeutic drugs, especially considering the chronic effect.

The data presented here are related to the research paper entitled âPCL-b-P(MMA-co-DMAEMA)2 new triblock copolymer for novel pH-sensitive nanocapsules intended for drug delivery to tumorsâ by Franco et al. [1]. Characterization data of PCL-diol, macroinitiator Br-PCL-Br, homopolymers (PMMA and PDMAEMA) and copolymers (batch 1 and batch 2) analyzed by FTIR, SEC and NMR, as well as, characterization of PCL-NS formulation by laser diffraction and DLS analysis, initial nanocapsule formulations and 1C-NC and 2C-NC formulations, including hydrodynamic diameter at different pH media, and DMSO cytotoxicity. Keywords: Methacrylic copolymer, Polycaprolactone, Nanocapsules, pH-sensitive, Cell viability

Lipid-core nanocapsules loaded with β-carotene and α-carotene, and lutein (NCs) were produced with monomodal particle size distribution. Their mean diameter was 151.33 ± 5.03 nm (D 4,3 ) and 180.30 ± 0.70 nm ( z -average), zeta potential was −22.63 ± 0.52 mV, and pH was 3.21 ± 0.04. The stability of NCs was studied under different simulated industrial treatments, such as thermal and ultraviolet (UV)–visible light treatment. Regardless of the temperature and incubation time of the samples, higher carotenoids retention (%) was observed in NCs than ethanol extract (EE) (under UV–vis light treatment) and higher carotenoids retention (%) was observed in NCs compared to EE and data already published on the stability of non-encapsulated carotenoids (under thermal treatment). In addition, NCs when exposed to UV–vis light treatment had higher activation energy and lower constant rate ( k ) than EE. In conclusion, nanoencapsulation offers greater stability to the β-carotene, α-carotene, and lutein upon exposure to conditions similar to those used in the food processing (heat) and storage (UV–vis light).

Carine C Drewes,1 Aline de CS Alves,2,3 Cristina B Hebeda,1 Isabela Copetti,2,3 Silvana Sandri,1 Mayara K Uchiyama,4 Koiti Araki,4 Silvia S Guterres,2 Adriana R Pohlmann,2,3 Sandra H Farsky1 1Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, 2Postgraduate Program in Pharmaceutical Sciences, 3Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, 4Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil Abstract: Metastatic melanoma is an aggressive cancer with increasing incidence and limited therapies in advanced stages. Systemic neutrophilia or abundant neutrophils in the tumor contribute toward its worst prognosis, and the interplay of cancer and the immune system has been shown in tumor development and metastasis. We recently showed the in vivo efficacy of poly(ε-caprolactone) lipid-core nanocapsule (LNC) or LNC loaded with acetyleugenol (AcE-LNC) to treat B16F10-induced melanoma in mice. In this study, we investigated whether LNC or AcE-LNC toxicity could involve modifications on crosstalk of melanoma cells and neutrophils. Therefore, melanoma cells (B16F10) were pretreated with vehicle, LNC, AcE or AcE-LNC for 24h, washed and, further, cocultured for 18h with peritoneal neutrophils obtained from C57Bl/6 mice. Melanoma cells were able to internalize the LNC or AcE-LNC after 2h of incubation. LNC or AcE-LNC pretreatments did not cause melanoma cells death, but led melanoma cells to be more susceptible to death in serum deprivation or hypoxia or in the presence of neutrophils. Interestingly, the production of reactive oxygen species (ROS), which causes cell death, was increased by neutrophils in the presence of LNC- and AcE-LNC-pretreated melanoma cells. LNC or AcE-LNC treatments reduced the concentration of transforming growth factor-β (TGF-β) in the supernatant of melanoma cells, a known factor secreted by cancer cells to induce pro-tumoral actions of neutrophils in the tumor microenvironment. Inaddition, we found reduced levels of pro-tumoral chemical mediators VEGF, arginase-1, interleukin-10 (IL-10) and matrix metalloproteinase-9 (MMP-9) in the supernatant of LNC or AcE-LNC-pretreated melanoma cells and cocultured with neutrophils. Overall, our data show that the uptake of LNC or AcE-LNC by melanoma cells affects intracellular mechanisms leading to more susceptibility to death and also signals higher neutrophil antitumoral activity. Keywords: hypoxia, serum deprivation, apoptosis, coculture, tumor microenvironment, LNC, acetyleugenol, intravital microscopy

Statins are used for the primary and secondary prevention of cardiovascular disease by inhibiting cholesterol synthesis in the liver. Statins have also noncholesterol-related effects, called pleiotropic effects, which arise from statins’ anti-inflammatory, immunomodulatory and antioxidant properties. These effects are especially attractive for the treatment of various brain diseases ranging from stroke to neurodegenerative diseases. Still, low brain concentrations after oral drug administration hinder the clinical application of statins in these pathologies. Pharmaceutical nanotechnologies may offer a solution to this problem, as local or targeted delivery of nanoencapsulated statins may increase brain availability. This special report rapidly summarizes the potential of statins in the treatment of brain diseases and the pharmaceutical nanotechnologies that could provide a viable approach to enable these indications.

Treatment of bacterial airway infections is essential for cystic fibrosis therapy. However, effectiveness of antibacterial treatment is limited as bacteria inside the mucus are protected from antibiotics and immune response. To overcome this biological barrier, ciprofloxacin was loaded into lipid-core nanocapsules (LNC) for high mucus permeability, sustained release and antibacterial activity. Ciprofloxacin-loaded LNC with a mean size of 180nm showed a by 50% increased drug permeation through mucus. In bacterial growth assays, the drug in the LNC had similar minimum inhibitory concentrations as the free drug in P. aeruginosa and S. aureus. Interestingly, formation of biofilm-like aggregates, which were observed for S. aureus treated with free ciprofloxacin, was avoided by exposure to LNC. With the combined advantages over the non-encapsulated drug, ciprofloxacin-loaded LNC represent a promising drug delivery system with the prospect of an improved antibiotic therapy in cystic fibrosis.