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Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata. Reversal of alopecia areata with topical TFB NPs treatment by blocking the JAK-STAT signaling pathways, reduced the expression levels of IFN-γ and the frequencies of NKG2D+CD8+ T cells, restored immune environment and promoted hair regrowth. [Display omitted] • Ex vivo mouse hair follicles model was used to assess formulations. • Hair follicles blocked skin model was used to evaluate drug permeation. • Cationic nanostructured carriers minimize systemic circulation and maximize hair follicle targeting. • The formulation restored immune privilege and ensured safe topical delivery for the treatment of alopecia areata. [ABSTRACT FROM AUTHOR]

The main objective of the experiment is to develop and evaluate hydrogel-bearing nanostructured lipid carriers (NLCs) loaded with ketoconazole (KTZ) for the effective treatment of candidiasis. The eugenol was used as a liquid lipid (excipient) for the development of KTZ-loaded NLCs and was explored for anti-fungal effect. The production of NLCs involves high energy processes to generate spherical, uniform particles, having a higher percentage of entrapment efficiency (%EE) for KTZ with 89.83 ± 2.31 %. The data from differential scanning calorimeter (DSC), powder x-ray diffraction (PXRD), and attenuated total reflectance (ATR) demonstrated the KTZ dispersion in NLCs. The NLCs loaded hydrogel possessed optimum spreadability and exhibited shear thinning behavior, indicating the ease of application of the final formulation. The 6.41-fold higher transdermal flux (Jss) was governed for KTZ from KTZ-NLC than coarse-KTZ, which explains the usefulness of NLCs. The KTZ-NLCs exhibited significant 2.58 and 6.35-fold higher retention in the stratum corneum and viable epidermis of the skin. The cell cytotoxicity studies using human dermal fibroblast cell (HDFS) lines depicted the usefulness of NLCs in reducing cell toxicities for KTZ. The KTZ-NLCs were found to inhibit planktonic growth and hyphal transition and showed a larger zone of inhibition against C. albicans strains with a MIC-50 value of 0.39 μg/mL. The antibiofilm activity of KTZ-NLCs at lower concentrations, in contrast to plain KTZ, explained the interaction of developed NLCs with fungal membranes. The overall results depicted the effectiveness of the loading KTZ in the lipid matrix to achieve antifungal activity against C. albicans. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, a novel bioadhesive material, a conjugate of chondroitin sulfate and L-cysteine (CS-Cys), was synthesized and modified on the surface of the cationic nanostructured lipid carriers loaded dexamethasone to prepare a novel nano-lipid ocular delivery system (Dex-CS-Cys-cNLC). Through the permeation and retention studies of isolated cornea, it was demonstrated that Dex-CS-Cys-cNLC has better corneal permeation and retention ability and can better overcome the barrier effect of the ocular surface. In addition, the fluorescent probe (RhB) was used to replace the drug, and fluorescence imaging was used to investigate the ocular surface retention ability of the formulation, and the results showed that CS-Cys-cNLC has stronger retention ability and can effectively prolong the time of drug action in the ocular surface. Dex-CS-Cys-cNLC was not irritating to rabbit eye tissues and was a safe delivery system. The results of rabbit dry eye pharmacodynamic experiments also showed that Dex-CS-Cys-cNLC could effectively alleviate dry eye symptoms in rabbits, effectively repair corneal damage, and improve the stability of tear film. All these experimental results suggest that Dex-CS-Cys-cNLC is a promising drug delivery carrier for the treatment of anterior segment of the eye disease. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina. [ABSTRACT FROM AUTHOR]

• RP-HPLC method for mesalamine (Mes) and curcumin (Cur) was developed • The developed method was validated as per ICH Q2 (R1) guidelines • Recovery above 95% and % RSD less than 2 indicated about accuracy and precision of method • Absence of interfering peaks at the retention times of Mes and Cur indicated method's specificity • The method was used to find drug loading, entrapment efficiency and drug release in Nano Structured Lipid Carriers The aim of this study was to develop simple, advance, accurate and precise method for the quantification of mesalamine (Mes) and curcumin (Cur) in nanostructured lipid carriers (NLCs) by using high Performance Liquid Chromatography (HPLC) technique. The analysis of the method was done by using C-18 Nucleodur column with 250 mm x 4.6 mm dimensions and having i.d. of 5µ. The quantification of Mes and Cur on HPLC was done by using mobile phase acetonitrile and water in the different ratios at different time intervals (gradient method), flow rate kept 1 mL/min and wavelength was set up at isosbestic point 365 nm. By using gradient method of ACN and water the peak of Mes and Cur was found to be at 1.7 min and 9.6 min respectively. The developed method was validated in accordance with ICH Q2 (R1) guidelines. The developed method showed linearity in the range of 2-10 ppm with r2 equals to 1 i.e 0.9998 for Mes and 0.9998 for Cur. The system suitability parameters of the method were also measured which were found to be tailing factor less than 2, resolution between Mes and Cur peaks was more than two and theoretical plates more than 2000. The LOD and LOQ of the developed method for Mes was found to be 0.14 µg/mL and 0.45 µg/mL. Whereas, LOD and LOQ of the developed method for Cur was found to be 0.17 µg/mL and 0.52 µg/mL respectively. The relative standard deviation of the developed method for both Mes and Cur were below 2 and percentage recovery was found to be between 95-105%. The robustness of the developed method was also checked by doing small changes in the flow rate and wavelength. The results of robustness study revealed that relative standard deviation and percentage recovery for both Mes and Cur were under acceptance criteria of ICH Q2 (R1) guidelines. This indicated that the method is precise, accurate, simple and robust. In addition, the developed method was effectively used for the estimation of entrapment efficiency (EE), drug loading (DL) and in vitro drug release study of Mes and Cur in the prepared Mes-Cur based NLCs. The EE of Mes and Cur in NLCs was found to be 99% and 84% respectively. Whereas, DL of Mes and Cur in the formulation was found to be 0.0019% and 0.0033% respectively. The in vitro drug release study showed that within 48h 100% Mes was released from NLCs. Whereas, 82.23% Cur was released from the NLCs. [ABSTRACT FROM AUTHOR]

The ability of chitosan (CTS) to promote mucoadhesion, trigger positive/negative surface interactions, and open tight junctions has inspired researchers to coat lipid-based and polymeric-based nanoparticles with CTS in an attempt to reach new heights in the delivery of drugs and nutraceuticals across different routes. This article discusses literature relevant to the pharmaceutical and biomedical area published in the last 10 years on nanoparticles overlaid with CTS. Herein, we addressed the technical aspects of the coating procedure by adding CTS solution to nanoparticles that have already been produced or during the production phase. Besides, we reviewed the applications of CTS coated nanoparticles as drug delivery systems in the oral and non-oral routes of administrations. Special attention was paid to the physicochemical and biological benefits of the CTS coating, such as improving physicochemical stability, enhancing cell and tissue interactions, controlled drug release, and augmentation of active substance bioavailability and efficacy. Moreover, this review projects the current standing and future prospects of the delivery system. The future calls for more investigations on therapeutic proteins, genes and vaccines as potential cargos. Extensive studies on the merits of integrating CTS with hydropolymer-synthesized nanoparticles and using longer-chain and chemically-modified variants of CTS are also warranted. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Epilepsy is a highly prevalent neurological disease and valproic acid (VPA) is used as a first-line chronic treatment. However, this drug has poor oral bioavailability, which requires the administration of high doses, resulting in adverse effects. Alternative routes of VPA administration have therefore been investigated, such as the nose-to-brain route, which allows the drug to be transported directly from the nasal cavity to the brain. Here, the use of nanostructured lipid carriers (NLC) to encapsulate drugs administered in the nasal cavity has proved advantageous. The aim of this work was to optimise a mucoadhesive formulation of VPA-loaded NLC for intranasal administration to improve the treatment of epilepsy. The Design of Experiment (DoE) was used to optimise the formulation, starting with component optimisation using Mixture Design (MD), followed by optimisation of the manufacturing process parameters using Central Composite Design (CCD). The optimised VPA-loaded NLC had a particle size of 76.1 ± 2.8 nm, a polydispersity index of 0.190 ± 0.027, a zeta potential of 28.1 ± 2.0 mV and an encapsulation efficiency of 85.4 ± 0.8%. The in vitro release study showed VPA release from the NLC of 50 % after 6 h and 100 % after 24 h. The in vitro biocompatibility experiments in various cell lines have shown that the optimised VPA-loaded NLC formulation is safe up to 75 µg/mL, in neuronal (SH-SY5Y), nasal (RPMI 2650) and hepatic (HepG2) cells. Finally, the interaction of the optimised VPA-loaded NLC formulation with nasal mucus was investigated and mucoadhesive properties were observed. The results of this study suggest that the use of intranasal VPA-loaded NLC may be a promising alternative to promote VPA targeting to the brain, thereby improving bioavailability and minimising adverse effects. [ABSTRACT FROM AUTHOR]

Schematic representation of functional pattern of Magnolol-NLC against Chronic obstructive pulmonary disease. (Created with BioRender, agreement number: AI272U59N1). [Display omitted] Chronic obstructive pulmonary disease (COPD) is a prevalent lung condition characterized by airflow obstruction, disability, and high mortality rates. Magnolol (MA), known for its anti-inflammatory and antioxidant properties, holds the potential for alleviating COPD symptoms. However, MA faces challenges like poor aqueous solubility and low bioavailability. Herein MA-loaded nanostructured lipid carriers (MA-NLC) were prepared using emulsification and solvent evaporation. These carriers exhibited a particle size of (19.67 ± 0.36) nm, a polydispersity index of (0.21 ± 0.01), and a zeta potential of (−5.18 ± 0.69) mV. The fine particle fraction of MA-NLC was (68.90 ± 0.07)%, indicating minimal lung irritation and enhanced safety. Pulmonary delivery of MA-NLC via nebulizer actively targeted the diseased lung tissues, facilitated slow release, and overcame the challenges of low oral absorption and bioavailability associated with MA. This formulation prolonged the residence time of MA and optimized its therapeutic effect in pulmonary tissues. Upon pulmonary administration, MA-NLC effectively regulated inflammatory and oxidative stress markers in COPD models, demonstrating its potential as a promising therapeutic platform for COPD management. [ABSTRACT FROM AUTHOR]

[Display omitted] • NLC functionalized with chitosan had not yet been investigated in PTD. • Chitosan coating resulted in greater encapsulation efficiency and greater stability. • Coated NLC was biocompatible and promoted faster drug entry into the skin. • The photodynamic efficiency of coated NLC was unexpectedly lower than uncoated NLC. The objective of this study was to obtain optimized nanostructured lipid carriers (NLC) functionalized with chitosan containing chloroaluminum phthalocyanine (ClAlPc) as a photosensitizer. Initially, the optimization of the preparation method of the NLC was performed, where the influence of different surfactants such as PVA and Tween 80, as well as different solid lipids such as stearic acid and Glycerol Monostearate (GM) was evaluated. The formulation containing GM and PVA (NLC10) was considered promising. Following, by the adsorption method (NLC10q), the formulation was functionalized with chitosan and characterized. NLC10 and NLC10q presented sizes of 131.5 and 231.5 nm, and ZP of −24.30 and + 19.96 mV, respectively. The encapsulation efficiency of NLC10q was 96 %, higher than NLC10 (79 %). The formulations were able to promote significant cutaneous retention of ClAlPc, after 2 h and 4 h of the study, and showed to be non-toxic to fibroblasts (biocompatible). PDT in BF16-F10 melanoma resulted in reduced cell viability to 70 % and 50 % for NLC10 and NLCq, respectively. In view of the results obtained, NLC showed to be promising in the treatment of skin cancer through PDT. NLC10q showed higher encapsulation efficiency and stability than NLC10, but, contrary to what was expected, it presented lower photodynamic efficiency. [ABSTRACT FROM AUTHOR]

[Display omitted] The digestion behaviour of lipid-based nanocarriers (LNC) has a great impact on their oral drug delivery properties. In this study, various excipients including surfactants, glycerides and waxes, as well as various drug-delivery systems, namely self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were examined via the pH-stat lipolysis model. Lipolysis experiments with lipase and pancreatin revealed the highest release of fatty acids for medium chain glycerides, followed by long chain glycerides and surfactants. Waxes appeared to be poor substrates with a maximum digestion of up to 10% within 60 min. Within the group of surfactants, the enzymatic cleavage decreased in the following order: glycerol monostearate > polyoxyethylene (20) sorbitan monostearate > PEG-35 castor oil > sorbitan monostearate. After digestion experiments of the excipients, SEDDS, SLN and NLC with sizes between 30 and 300 nm were prepared. The size of almost all formulations was increasing during lipolysis and levelled off after approximately 15 min except for the SLN and NLC consisting of cetyl palmitate. SEDDS exceeded 6000 nm after some minutes and were almost completely hydrolysed by pancreatin. No significant difference was observed between comparable SLN and NLC but surfactant choice and selection of the lipid component had an impact on digestion. SLN and NLC with cetyl palmitate were only digested by 5% whereas particles with glyceryl distearate were decomposed by 40–80% within 60 min. Additionally, the digestion of the same SLN or NLC, only differing in the surfactant, was higher for SLN/NLC containing polyoxyethylene (20) sorbitan monostearate than PEG-35 castor oil. This observation might be explained by the higher PEG content of PEG-35 castor oil causing a more pronounced steric hindrance for the access of lipase. Generally, digestion experiments performed with pancreatin resulted in a higher digestion compared to lipase. According to these results, the digestion behaviour of LNC depends on both, the type of nanocarrier and on the excipients used for them. [ABSTRACT FROM AUTHOR]

Targeted-drug administration to liver reduces side effects by minimising drug distribution to non-target organs and increases therapeutic efficacy by boosting drug concentration in target cells. In this study, arabinogalactan-(AG), pullulan-(PL) and lactobionic acid-(LA) were selected as natural ligands to target asialoglycoprotein receptor-(ASGPR-1) present on hepatocytes. In silico docking studies were performed and binding affinities of novel ligands viz. palmitoylated AG-(PAG), lauroylated AG-(LAG), palmitoylated PL-(PPL), lauroylated PL-(LPL) and lactobionic acid–adipic acid dihydrazide conjugate-(LAD) were compared with AG, PL and LA. These novel ligands were successfully synthesized and characterized. The ligands were incorporated into drug loaded nanostructured lipid carriers-(NLCs) for surface functionalization. HepG2 cellular internalization of hepatocyte-targeted NLCs was studied using fluorescence microscopy and LAD-decorated-drug loaded NLCs giving maximum cellular uptake were studied using confocal microscopy. Toxicity potential of LAD-decorated NLCs was assessed in vivo. Molecular docking results suggested that among the ligands, order of binding affinity was found to be LAD>PAG > PPL > LPL > LAG. Acute toxicity studies revealed hemocompatibility and absence of organ toxicity for ligand LAD. Additionally, the results establish proof-of-concept of enhanced targeting efficacy of novel ASGPR targeting ligands. These ligands can be used for surface modification of nanocarriers for future targeted delivery in treating various liver disorders. [Display omitted] • Molecular docking studies of novel ligands with ASGPR target protein • Synthesis, characterization of ligands, design of ligand anchored drug loaded NLCs • In vitro HepG2 uptake and in vivo acute toxicity study in Swiss albino mice • LAD decorated drug loaded NLCs gave maximum HepG2 cellular uptake • Establishes proof of concept of enhanced efficacy of novel ASGPR targeting ligands [ABSTRACT FROM AUTHOR]

• The clinical application of siRNA for brain disease therapy remains a big challenge. • The siRNA based gene silencing technology has proven potential for treatment of NDs. • Nanocarriers can provide promising opportunities for improving NDs. • We highlighted the role of nanocarriers for the treatment of NDs. Neurodegenerative disorders (NDs) lead to the progressive degeneration of the structural and physiological functions of the central and peripheral nervous systems, resulting in lifelong cognitive and motor dysfunction. Although comprehensive treatment of NDs is lacking, small interfering (si)RNA has shown therapeutic utility in the form of cellular nuclease-driven downregulation of mRNA levels. Various nanotechnologies have been used to modulate crucial physicochemical and biopharmaceutical properties of siRNA to provide protection and to enhance biomembrane interactions, residence times, tissue absorption, and cellular internalization for improved cytoplasm and/or nucleus interactions. In this review, we highlight advances in, and the role of, siRNA-based nanocarriers for the treatment of various NDs. [ABSTRACT FROM AUTHOR]

Oral conditions, such as recurrent aphthous stomatitis, are chronic inflammatory disorders that significantly affect the life quality. This study aims to develop a novel buccal mucoadhesive based on methacrylate hydroxypropyl methylcellulose (M-HPMC) and methacrylate lignin (M-SLS) encapsulated with nanostructured lipid carriers (NLCs) for controlled release of alpha-pinene (α-pinene). NLCs with particle sizes of 152 ± 3 nm were prepared by using stearic acid and oleic acid as solid and liquid lipids, respectively. Following the successful synthesis of M-HPMC and M-SLS, various concentrations of α-pinene loaded NLCs (0, 18, 38, and 50 wt%) were encapsulated in M-HPMC/M-SLS hydrogel. It was demonstrated that the physiological and mechanical performances of hydrogels were changed, depending on the NLC content. Remarkably, the incorporation of 18 wt% NLC improved the compressive strength (143 ± 14 kPa) and toughness (17 ± 1 kJ/m3) of M-HPMC/M-SLS hydrogel. This nanocomposite hydrogel considerably decreased dissipated energy from 1.64 kJ/m3 to 0.99 kJ/m3, after a five-cycle compression test. The nanocomposite hydrogel exhibited controlled α-pinene release for up to 96 h which could significantly improve the antioxidant activity of M-HPMC/M-SLS matrix. Moreover, the reinforcing M-HPMC/M-SLS hydrogel with α-pinene-loaded NLCs resulted in increased adhesive strength (113.5 ± 7.5 kPa) to bovine buccal mucosa and cytocompatibility in contact with fibroblasts. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Nanoparticles exhibited suitable physicochemical parameters and sustained release. • Nanoparticles were internalized inside ocular cells. • Nanoparticles decreased ocular inflammation in vivo. • Nanoparticles were able to revert dry eye symptoms and ameliorate corneal lesions. Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation. [ABSTRACT FROM AUTHOR]

The present study aimed to develop novel masculinization agents for enhancing sex-reversal in red tilapia (Oreochromis sp.) by immersion administration using 17α-methyltestosterone-loaded nanostructured lipid carriers (MT-NLC). Moreover, the surface charge of the MT-NLC was modified with chitosan (CS-MT-NLC) to improve their mucoadhesive property. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to characterize the morphology of the nanoparticles. Furthermore, we assessed the toxicity associated with immersion-induced masculinization in red tilapia. Subsequently, we examined alterations in gill morphology, determined the percentage of masculinization, analyzed their length-weight relationship, and investigated the expression of genes related to sex differentiation. MT-NLC had an average size, polydispersity index, and negatively charged surface of 140.8 ± 2.6 nm, <0.2, and −26.9 ± 0.3 mV, respectively, with higher stability at 4 °C and 25 °C compared to CS-MT-NLC. The release mechanisms of NLC and CS-NLC were regulated by diffusion processes, which were characterized using Avrami's equation. In contrast, the release mechanism of non-encapsulated MT (MT-ET) was governed by burst release kinetic. Furthermore, tests assessing mucin binding confirmed that CS-MT-NLC, with a positive charge, exhibited superior mucoadhesive properties compared to MT-NLC, with a negative charge. Importantly, CS-MT-NLC immersion was found to be toxic to red tilapia fry; therefore, it has been discontinued for further experiments. The immersions of both MT-NLC and MT-ET were non-toxic to red tilapia fry, with an LC 50 exceeding 800 μg/L, and the morphological appearance of the gills after treatment was normal. The MT-NLC-400 and MT-ET-800 groups exhibited elevated expression levels of dmrt1 and sox9 compared to cyp19a1a and soxl2. These higher expression levels corresponded to significantly higher percentages of males (98.3% and 95.7%) in both the MT-NLC and MT-ET groups compared to the control group (54.7%). The MT-NLC and MT-ET groups displayed a negative allometric growth behavior in red tilapia fry, with a relative condition factor > 1. Adopting MT-NLC-400 immersion treatment for masculinizing red tilapia could serve as a beneficial strategy for commercial tilapia farms to reduce the required dosage and the time needed to treat fish. • Novel masculinization agents for enhancing sex-reversal efficiency in red tilapia by immersion using17α-alpha-methyltestosterone-loaded nanostructured lipid carriers (MT-NLC). • MT-NLC showed140.8 nm avg. size, <0.2 polydispersity index, and −26.9mV surface charge, with improved stability at cool and ambient temps. • Red tilapia fry exhibited no toxicity to MT-NLC and MT-ethanol (MT-ET) treatments by immersion, with LC 50 >800 μg/L and normal gill morphology. • MT-NLC-400 obtained 98.3% males with heightened expressions of dmrt1 and sox9 , compared to 54.7% males in control. • Red tilapia farming can use MT-NLC-400 immersion to reduce the dose and duration of MT treatment for masculinization. [ABSTRACT FROM AUTHOR]

[Display omitted] Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX as smart chemotherapy to improve its photostability and anticancer efficacy. The characteristics of DOX and DOX-loaded NLCs were investigated using UV–Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, particle size, and zeta potential study. The cytotoxicity of DOX was evaluated against three cancer cell lines (HeLa, A549, and CT-26). The particle size and zeta potential were in the range 58.45-94.08 nm and −5.80 mV - −18.27 mV, respectively. The chemical interactions, particularly hydrogen bonding and van der Waals forces, between DOX and the main components of NLCs was confirmed by FTIR. NLCs showed the sustained release profile of DOX. The photostability results revealed that the NLC system improved the photostability of DOX. Cytotoxicity results using the three cell lines showed that all formulations improved the anticancer efficacy of free DOX, and the efficacy was dependent on cell type and particle size. These results suggest that DOX-loaded NLCs are promising chemotherapeutic agents for cancer treatment. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is known to activate poly (ADP-ribose) polymerase (PARP-1), which leads to pronounced negative effects on mitochondrial DNA (mt-DNA) repair and function. Notably, PARP inhibitors are reported to be beneficial in experimental models of TBI. A targeting strategy for the delivery of neuronal mitochondria-specific PARP inhibitors could result in a greater neuroprotective effect and be a safer approach for TBI treatment. In the present study, we developed the PARP inhibitor olaparib (Ola) as a model drug and devised red blood cell (RBC)-coated nanostructured lipid carriers (RBCNLCs) co-modified with C3 and SS31 peptide (C3/SS31-RBCNLCs) for brain neuronal mitochondria-targeting. Our results indicated that biomimetic nanosystems have the physical and chemical properties of the NLCs, as well as the biological properties of RBC. A high concentration of Ola delivered into brain mitochondria by C3/SS31-RBCNLCs-Ola effectively improved mitochondrial function and prevented neuronal cell death caused by excessive activation of injury-induced mitochondrial PARP (mt-PARP) in vitro and in vivo. Taken together, the results of this study support the preclinical feasibility of developing highly effective nano-drugs as part of precision medicine for TBI. TBI-induced neuronal mitochondria DNA damage activates Poly(ADP-ribose) Polymerase (PARP1) which leads to a pronounced negative effect on mitochondrial DNA repair and mitochondrial function. In recent years, PARP inhibitors showed strong benefits in experimental models of TBI, more importantly PARP inhibitors specially target neuronal mitochondria may play a greater neuroprotective role and may be a safer approach for TBI treatment. Herein, we designed red blood cell (RBC) membrane-coated nanostructure lipid carriers dual-modified with C3 and SS31 (C3/SS31-RBCNLCs) to accomplish these objectives. After encapsulating Olaparib (Ola) as the model PARP inhibitor, the data demonstrated that C3/SS31-RBCNLCs, with brain neuronal mitochondria targeting, can reduce neuronal cell death and improve mitochondrial dysfunction triggered by mitochondrial PARP activation in vitro and in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

As immune adjuvants assisting vaccines, nanoparticle delivery systems have been widely exploited. Squalene, the major ingredient of approved adjuvant MF59, has great potential in activating immune responses. In the current study, model antigen ovalbumin (OVA) was encapsulated into squalene-based nanostructured lipid carriers (NLCs), and the chitosan, a cationic polysaccharide, was used for modifying nanoparticles to develop a functionalized and cationic nanoparticle delivery system (OVA-csNLCs). Firstly, the optimal formulation of csNLCs was successfully screened out, and had hydrodynamic diameter of 235.80 ± 5.99 nm and zeta potential of 34.90 ± 6.95 mV. Then, the generated OVA-csNLCs had no significant difference in hydrodynamic diameter and exhibited lower zeta potential of 19.03 ± 0.31 mV and high encapsulation efficiency of 83.4%. Sucrose (10%, w /w) was selected as optimal lyoprotectant, exhibiting good stability of OVA-csNLCs in the form of freeze-dried powder. More importantly, the OVA-csNLCs effectively promoted OVA antigen uptake by macrophage, significantly enhanced the level of OVA-specific IgG, and induced a Th2-based immune response in vivo. Furthermore, mice immunization experiment demonstrated that OVA-csNLCs had well biocompatibility and facilitated spleen lymphocytes proliferation. Above findings indicate that chitosan modified squalene nanostructured lipid carriers show promise as antigen delivery system and an open adjuvant platform. [ABSTRACT FROM AUTHOR]

The high incidence and costs of chronic wounds in the elderly have motivated the search for innovations to improve product performance and the healing process while reducing costs. In this study, bioadhesive nanostructured lipid carriers (NLC) were developed for the co-encapsulation of compounds with antioxidant (α-tocopherol and quercetin) and antimicrobial (tea tree oil) activity for management of wounds. The NLC was produced with shea butter and argan oil, and modified with sodium alginate or chitosan to confer bioadhesive properties. Spherical nanoparticles of ~307–330 nm and zeta potential varying from −21.2 to +11.8 mV were obtained. Thermal analysis demonstrated that the lipid matrix reduced tea tree oil thermal loss (~1.8-fold). Regardless of the type of polysaccharide employed, the NLCs promoted cutaneous localization of antioxidants in damaged (subjected to incision) skin, with a ~74 to 180-fold higher delivery into the skin compared to percutaneous delivery. This result is consistent with the similar bioadhesive properties of chitosan or sodium alginate-modified NLC. Nanoencapsulation of tea tree oil did not preclude its antimicrobial effects against susceptible and resistant strains of S. aureus and P. aeruginosa , while co-encapsulation of antioxidants increased the NLC-induced fibroblasts migration, supporting their potential usefulness for management of wounds. • Developed shea butter and argan oil-based nanostructured lipid carriers (NLC) • Coating with chitosan (Ch) or sodium alginate (Al) conferred opposite charges • Encapsulation of tea tree oil reduced its thermal loss and did not preclude antimicrobial effects • Regardless of the polysaccharide, NLC provided cutaneous targeting • NLC increased fibroblast migration, and antioxidants encapsulation intensified the effect. [ABSTRACT FROM AUTHOR]

• Capsaicinoids from chili plants have anti-inflammatory and analgesic properties. • In vitro and in vivo tests show capsaicinoids' secondary effects topically. • Nano-sized delivered capsaicinoids show reduced secondary effects. • Nano-sized capsaicinoids show enhanced anti-inflammatory and analgesic properties. • There are few in vitro and in vivo tests using nano-sized delivered capsaicinoids. Capsaicinoids confer the pungency in chili peppers and are proven to contain many beneficial traits, among them analgesic and anti-inflammatory properties. Capsaicinoids produce a burning sensation when administered and have other secondary effects given their pungency. This is why many drug delivery vehicles have been tested to prove their efficacy in reducing the secondary effects of these compounds while still having its primary beneficial effects. There are many articles that talk about the formulation of drug delivery systems and their properties yet there is little information on the therapeutic effects of applying these drug delivery systems. This review is focused on studies' results that prove efficacy of capsaicinoids specially in those that use them in nano-sized drug delivery systems. Nano-sized carriers have been proven to reduce the secondary effects of capsaicinoids while improving the bioavailability, absorption, anti-inflammatory and analgesic properties of these compounds. [ABSTRACT FROM AUTHOR]

Early treatment with parenteral antimalarials is key in preventing deaths and complications associated with severe and cerebral malaria. This can be challenging in 'hard-to-reach' areas in Africa where transit time to hospitals with facilities to administer drugs parenterally can be more than 6 h. Consequently, the World Health Organization has recommended the use of artesunate (ATS) suppositories for emergency treatment of patients, however, this treatment is only for children under 6 years. The intranasal route (INR) can provide a safe and effective alternative to parenteral and rectal routes for patients of all ages; thus, reducing delays to the initiation of treatment. Hence, we designed ATS-loaded nanostructured lipid carriers (NLCs) for intranasal administration. ATS-NLCs were formulated using varying concentrations of lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising a 1:2 ratio of Phospholipon ® 90H and lipids (Softisan ® 154 or Compritol ®). ATS-NLCs were spherical, and the small sizes of ATS-NLCs obtained for some formulations (76.56 ± 1.04 nm) is an indication that ATS-NLCs can pass through the nasal mucosa and reach the brain or systemic circulation. Encapsulation efficiency of ATS in NLCs was ≥70% for all formulations. ATS-NLCs achieved up to 40% in vitro drug release in 1 h, while ex vivo permeation studies revealed that formulating ATS as NLCs enhanced permeation through pig nasal mucosa better than drug solution. Most importantly, the activity and reduction in parasitaemia [in mice infected with P lasmodium berghei ANKA in a murine cerebral malaria model] by ATS-NLCs administered through the INR (54.70%, 33.28%) was comparable to intramuscular administration (58.80%, 42.18%), respectively. Therefore, intranasal administration of NLCs of ATS has great potentials to serve as a satisfactory alternative to parenteral administration for the treatment of severe and cerebral malaria in both adults and children in remote areas of sub-Saharan Africa. [Display omitted] • High encapsulation of a hydrophilic drug (artesunate (ATS) in nanostructured lipid carriers (NLCs) can be achieved by using solidified reverse micellar solutions as solid lipid. • Encapsulating ATS in NLCs improved ex vivo permeation better than simple drug solution. • Intranasal administration of ATS-NLCs had comparable outcomes as intramuscular administration in the treatment of severe malaria in mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • Internal structural modulation of nanostructured lipid carriers (NLC). • Hydrogenated soybean phospholipid hindered the NLC polymorphic transition. • Ester bond number of solid lipid affected the crystallization of NLC. In this current study, the internal structure of nanostructured lipid carriers was modulated by phospholipids (lecithin PC, hydrogenated soybean phospholipid HPC) and solid lipids to achieve stable encapsulation of citral. The presence of high melting point HPC could construct α-crystalline type with more lattice defects and effectively inhibit β-ization. The HPC group could maintain the particle size at 155.9–186.9 nm, the polydispersity index (PDI) at 0.182–0.321, the Zeta potential at −57.58 mV to −49.35 mV and the retention rate of citral at 91.33–98.49 % in the acidic environments of 2 mM and 20 mM hydrochloric acid solutions. The recrystallization index (RI) of NLC increased with the number of solid lipid ester bonds (from 3.57 % to 16.58 % in the PC group and from 0.82 % to 12.47 % in the HPC group). The results illustrated that the number of solid lipid ester bonds and the melting point of phospholipids affected crystallinity of the lipid matrix and thus the stability of encapsulated citral. Hydrogenated phospholipid with high melting points was more beneficial in stabilizing citral. The present study improved the acidic stability of citral and provided a new thought for the application of citral in acidic beverages. [ABSTRACT FROM AUTHOR]

[Display omitted] • Development nanostructured lipid carriers using quality by design approach. • A sensitive and eco-friendly spectrofluorimetric method for estimation of IBR. • Comprehensive strategy of white analytical chemistry and AQbD approach. • In-vitro drug release kinetic and in-vitro drug release kinetic study of IBR-NLCs. • Assessment of methods using RGB model, AGREE, ESA, NEMI and GAPI metrics. Ibrutinib (IBR) is a drug classified as BCS class II, characterized by low solubility and high permeability. However, its oral bioavailability is limited to a mere 2.9% due to significant first-pass metabolism. To address this challenge, researchers developed IBR-NLCs (Nanostructured Lipid Carriers) using a DoE-based hot melted ultrasonication method to enhance its bioavailability and drug release profile. While various methods exist for IBR analysis in pharmaceutical formulations, human plasma, and rat plasma, a sensitive spectrofluorimetric method has not been reported for estimating IBR. To facilitate in-vitro drug release kinetic studies of IBR-NLCs, a sensitive and green spectrofluorimetric method was developed, combining principles of white analytical chemistry and analytical quality by design. This approach included a fractional factorial design for screening of method variables and a Box-Behnken design for method optimization. The developed method underwent rigorous validation following ICH guidelines. The developed method was applied to assess the in-vitro drug release kinetic study of IBR-NLCs in comparison to marketed formulations. Remarkably, the optimized IBR-NLCs exhibited sustained release of IBR which helps to decrease dose and dose frequency. The whiteness and greenness profiles of published and proposed method have been assessed using analytical greenness calculator, green analytical procedure index software, national environmental method index standards, and eco-scale assessment tool. The results confirmed that the proposed method is sensitive, eco-friendly, cost-effective, speedy, and user-friendly, making it an excellent choice for IBR estimation in NLCs. In summary, the developed method for drug release kinetic study of BR-NLCs, utilizing principles of white analytical chemistry and analytical quality by design, has not only improved drug release profile but also resulted in an efficient and environmentally friendly analytical approach. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pickering emulsions were constructed with different NLCs as colloidal particles. • PE stabilized with D-NLCs and C-NLCs exhibited an inversion from W/O to O/W. • The inversion occurred when the volume fraction of NLCs increased to 50%. • PE stabilized with 50% D-NLCs exhibited optimal stability. Three types of curcumin-loaded nanostructured lipid carriers with a single layer (S-NLCs), double layer (D-NLCs) and composite layer (C-NLCs) were used as stabilizers for the preparation of Pickering emulsions. Visual observations showed that the NLCs stabilized the Pickering emulsions at different addition volume fractions. The emulsions produced had approximate particle size and showed an inversion of the emulsions stabilized by D-NLCs and C-NLCs as the additional fraction of NLCs was increased to 50%. Contact angles and interfacial viscoelasticity showed a better wetting of D-NLCs with a superior ability to reduce surface tension at the oil–water interface. Pickering emulsions stabilized at a 50% volume ratio (PD5) showed the highest storage and centrifugal stability. Simulated in vitro digestion studies showed the presence of delayed lipid digestion of Pickering emulsions, resulting in the incomplete release of curcumin and lower bioavailability than NLCs under the same conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] Acne constitutes one of the most prevalent skin disorder affecting both skin and mental health of patients. However, no cure has been developed so far. In this area, Thymol constitutes a potential candidate since it is able to restore the healthy microbiota of the skin. However, its permeation properties cause its fast elimination and, to avoid this problem, thymol has been loaded into nanostructured lipid carriers (TH-NLCs). Moreover, to increase the suitability of these systems for skin applications, several surface functionalization strategies of TH-NLCs had been assessed. Among the different molecules, phosphatidylcholine-TH-NLCs demonstrated to be safe as well as to provide high antioxidant activity in cellular studies. Therefore, to administer these systems to the skin, functionalized TH-NLCs were dispersed into a carbomer gel developing semi-solid formulations. Rheological properties, porosity and extensibility of TH dispersed in carbomer as well as phosphatidylcholine-TH-NLCs were assessed demonstrating suitable properties for dermal applications. Moreover, both formulations were applied in healthy volunteers demonstrating that gel-phosphatidylcholine-TH-NLCs were able to increase in skin hydration, decrease water loss and reduce skin sebum. Therefore, gel-phosphatidylcholine-TH-NLCs proved to be a suitable system for skin pathologies linked with high sebum generation, loss of hydration and high oxidation, such as acne vulgaris. [ABSTRACT FROM AUTHOR]

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers (SLNs, NLCs and NEs) for nose-to-brain delivery. Based on the literature available from the past two years, we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration. The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out. Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear, it appears that the intranasal route together with the use of NLCs, SLNs or NEs is advantageous for targeting drugs to the brain. These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs, so they are expected to be approved by regulatory authorities in the coming years. Intranasal delivery of nanostructured lipid carriers (NLC), solid lipid nanoparticles (SLN) and nanoemulsions in rats and rabbits resulted in higher drug concentration in the brain, compared to blood, proving the effectiveness of nose-to-brain delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

Tamoxifen (TAM) and Sulphoraphane (SFN) are well-known anti-estrogen drugs used for the treatment of breast cancer. Due to their synergistic therapeutic potential, their combination is preferred as it helps to minimize the drug-related toxicities and enhances therapeutic efficacy. A simple, robust and fast simultaneous reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed as well validated for the analysis of both the drugs based on their particular wavelength. The separation was performed on C 18 analytical column with dimensions of 4.6 × 250 mm, 5 μm using mobile phase methanol: water (pH 3.5) in the ratio 70:30 and flow rate of 0.8 min/mL. Box-Behnken experimental design was used to optimized these independent variables and analyze their effect on the response variables like retention time (RT), no. of theoretical plates and tailing factor of both analytes. Method validation was carried out for establishing the specificity, linearity range, accuracy, sensitivity, robustness, precision and ruggedness. The method applicability was evaluated on different nanoformulations, i.e., solid lipid nanoparticles (SLNs), liposomes (LIPO), nanostructured lipid carriers (NLCs). The peaks of the analyte were found to be well resolved and two distinct RT were recorded for TAM and SFN. Calibration curves were found to be linear for TAM and SFN over concentration range of 6–24 μg/mL. All method validation criteria were within the range of acceptance. Relative standard deviation (%RSD) was observed to be <2% for inter- and intra-day precision. The application of developed method for estimation of drugs from the nanoformulations was suitabile for in vitro as well as in vivo studies. [ABSTRACT FROM AUTHOR]

The discovery of new alternatives for the treatment of infectious diseases has become the focus of burgeoning global interest. The complexation of the wide-spectrum antibiotic nalidixic acid (NA) with oxidovanadium(IV) ion and its incorporation into hybrid nanoparticulate systems were explored. The V-NA complex proved to be a stronger antimicrobial agent against E. coli , B. cereus , S. aureus and P. aeruginosa than NA, based on inhibition experiments. Myristyl myristate nanostructured lipid carriers (NLCs) and polymeric nanoparticles of Eudragit NE30D (EuNPs) were hybridized with chitosan (chi) to increase their stability and mucoadhesivity. They showed V-NA encapsulation of 97.8 ± 0.5% and 96.1 ± 0.1% respectively. TEM and DLS characterization ascertained the presence of spherical positive charged NPs ranging from 170 to 330 nm. Controlled release of V-NA from NPs was observed with 30–40% release in 3 days. A considerable potentiation of V-NA antimicrobial activity from 5 to 10 times was elucidated against P. aeruginosa with MIC values of 59.3 and 129.9 μM for NLC/chi and EuNPs/chi respectively, in comparison with 625 μM of the free complex. Hybrid NPs were able to interfere with the quorum sensing of the reporter Chromobacterium violaceum. Cytotoxicity on mouse fibroblast L929 cells was evaluated in the range of 29.7–519 μM by MTT assay showing that, NLC/chi particles supported cell growth in the range of at 29.7–60 μM while Eu/chi do not exert cytotoxicity between 29.7 and 120 μM. These results suggest that nanoparticles are suitable systems for drug delivery applications. Unlabelled Image • The vanadium-nalidixic acid complex shows strong antibacterial activity. • Nanoencapsulation of V-NA into EuNPs and NLCs enhances its antibacterial properties. • Hybrid chitosan polymeric/lipidic matrices show a controlled release of V-NA. • V-NA loaded NLCs and EuNPs exhibit anti- quorum sensing properties. • V-NA EuNPs show great cytocompatibility in mouse fibroblast L929 cells at MICs values. [ABSTRACT FROM AUTHOR]

Pulmonary delivery of lipid-based nanotherapeutics by inhalation presents an advantageous alternative to oral and intravenous routes of administration that avoids enzymatic degradation in gastrointestinal tract and hepatic first pass metabolism and also limits off-target adverse side effects upon heathy tissues. For lung-related indications, inhalation provides localized delivery in order to enhance therapeutic efficacy at the site of action. Optimization of physicochemical properties, selected drug and inhalation format can greatly influence the pharmacokinetic behavior of inhaled nanoparticle systems and their payloads. The present review analyzes a wide range of nanoparticle systems, their formulations and consequent effect on pharmacokinetic distribution of delivered active components after inhalation. Unlabelled Image [ABSTRACT FROM AUTHOR]

Oral Almotriptan maleate (ALM) is used in the treatment of migraine; however, due to its extreme aqueous solubility, shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. Being flexible and lipophilic in nature, nanostructured lipid carriers (NLCs) represent a promising tool in delivering therapeutic substances to the brain. This investigation is meant to explore the capability of mucoadhesive chitosan-coated NLCs to efficiently deliver ALM to the brain through the nasal route as a non-invasive alternative route for targeting the central nervous system (CNS). D-optimal design was adopted and thirteen different formulae were prepared using hot homogenization and ultrasonication technique; where an accurate amount of the almotriptan was added to the molten lipid mixture followed by the addition of the heated aqueous phase under stirring, then the mixture was subjected to homogenization and ultrasonication. The prepared systems were then assessed for their particle size, PDI (polydispersity index), zeta potential (ZP), and entrapment efficiency (EE). The optimized selected formula; F1; composed of 50/50 Compritol/Labrafil and a co-mixture of 2:1 tween 80: Lauroglycol all coated in chitosan, showed a PS of 255 nm, PDI 0.27, ZP 34.1 mV, and 80% EE. A bi-phasic in vitro drug release pattern was obtained, enhanced mucoadhesive property and ex-vivo permeability through sheep nasal mucosa were attained. The In vivo studies performed on albino rabbits showed significantly higher C max results in plasma of the optimized ALM-NLC (1.54 μg/mL) compared to those of IN ALM solution (0.25 μg/mL) and ALM oral tablet market product (0.58 μg/mL). Brain C max were found to be 3.64 μg/mL, 0.5 μg/mL and 0.48 μg/mL for IN ALM-NLC, oral ALM market product and, IN ALM solution, respectively. Histopathological examination marked the formula as safe. [ABSTRACT FROM AUTHOR]

Dry eye syndrome is a common eye disease that affects many people worldwide. It is usually treated with eye drops, which has low bioavailability owing to rapid clearance from the ocular surface and leads to poor patient compliance and side effects. For the purpose of improving the therapeutic efficacy, nanostructured lipid carrier (NLC)-loaded dexamethasone (DEX) was prepared and functionalized with (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS). As APBA has a boronic acid group, it can form a high-affinity complex with sialic acids present in the ocular mucin, which contributes to extension of corneal retention time and improvement of drug delivery. Compared with eye drops, Rhodamine B (RhB)-labeled APBA-ChS-NLC could significantly prolong the residence time on the corneal surface. Moreover, the DEX-APBA-ChS-NLC showed no irritation to the rabbit eye as indicated in irritation studies and histological images. The pharmacodynamics study indicated that DEX-APBA-ChS-NLC could relieve symptoms of dry eye disease in rabbits. These results demonstrated that the developed mucoadhesive drug carrier could improve the delivery of drugs and have promising potential to treat anterior eye diseases. In this research, (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS)-based nanostructured lipid carriers (NLCs) including dexamethasone (DEX) were designed and constructed. APBA-ChS, which is present on the surface of DEX-NLC and contains the boronic acid group, can form complex with sialic acids in the ocular mucin, hence leading to prolonged precorneal retention. This affinity between boronic acid and sialic acids was used to develop a mucoadhesive drug delivery system. The developed mucoadhesive drug carrier demonstrated prolonged retention time and alleviation of dry eye syndrome. APBA-ChS-based NLC may be considered a promising ocular drug delivery system for treating anterior eye diseases. [ABSTRACT FROM AUTHOR]

Antioxidant nutraceuticals can be found in several dietary sources and have been utilized for various medical benefits including health promotion, disease prevention, and support for treatment of acute and/or chronic diseases. Nonetheless, there are some limitations in delivering antioxidants via oral administration such as low solubility and permeability, pH and enzyme degradation, and instability of the compounds along the gastrointestinal tract leading to low bioavailability. In order to tackle these challenges, the utilization of lipid nanoparticles has numerous advantages to the escalating delivery system of antioxidants in nutraceuticals across the gastrointestinal tract barrier. Nowadays, several types of lipid nanoparticles can be used in antioxidant nutraceutical delivery systems through the oral route, namely solid lipid nanoparticles and nanostructured lipid carriers. This review article aims to provide notable information on the importance and applications of lipid nanoparticles in antioxidant delivery systems from nutraceuticals by an oral route. The mechanism in enhancing antioxidant compound transport across the gastrointestinal tract can occur by elevating loading capacity, improving chemical and physical stability, and increasing its bioavailability. To date, lipid nanoparticle vehicles have been developed to improve the delivery of antioxidant compounds to enhance bioavailability via oral routes. Lipid nanoparticles have remarkable benefits in delivering antioxidant nutraceuticals via oral administration. Hence, scale-up and commercialization of antioxidant nutraceutical-loaded lipid nanoparticles have been a potential technology in recent years. Subsequently, several vegetable and natural oils with antioxidant activity can also be utilized for nanoparticle formulation lipid components to increase nutraceuticals' antioxidant properties and bioavailability. [Display omitted] • Lipid nanoparticles enhanced oral bioavailability and stability of compounds. • Focuses on solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) • SLN and NLC were employed as carriers for delivering antioxidant nutraceuticals. • NLC was beneficial for higher entrapment efficiency, stability, and bioavailability. [ABSTRACT FROM AUTHOR]

Surface modification of nanostructured lipid carriers (NLCs) can be an effective way to improve their oral delivery for active ingredients. In this study, four type of guar gum series modified NLCs for the delivery of phytosterols (PS) were constructed and the effects of the polysaccharides on their structure and physicochemical properties were studied. DLS and AFM results revealed that positively charged polysaccharides could bind to PS-NLCs through electrostatic attraction and made the complexes finally take positive charges, while negatively charged polysaccharides were more likely to fill in the gaps of NLC systems to achieve a balance between electrostatic repulsion and intermolecular forces. Although all four polysaccharides exhibited good storage stability and controlled release of PS in simulated intestinal digestion, PS-NLCs modified with partially hydrolyzed cationic guar gum (PHCG) at medium or high concentrations exhibited better gastric stability, mucoadhesion, and cellular uptake, which had considerable significance for improving the oral bioavailability of PS. This might be related to the coating structure of PHCG-PS-NLCs confirmed by AFM, FTIR, and Raman characterization. This study provide a reference value for designing suitable PS-NLC complexes without synthetic surfactants. • Guar gum series affect on PS-NLC though molecular weight, charge, and viscosity. • Complexe stability is determined by the electrostatic repulsion and steric effect. • Positively charged complexes exhibit superior gastric stability and mucoadhesion. • Partially hydrolyzed cationic guar gum can tightly modify PS-NLC in a core-shell form. [ABSTRACT FROM AUTHOR]

The objective of this work was to develop nanostructured lipid carriers (NLCs) with preservation effect by using pea protein isolate (PPI) nanoparticles as emulsifiers, candelilla wax (CW) as organo-gelator and d -limonene (DL) as antifungal agent. The optimal formulation parameters of NLCs were firstly determined based on results of particle size, poly-dispersity index and zeta potential, and then NLCs prepared by optimal formulation were further characterized. The results showed that DL was successfully encapsulated inside NLCs. Moreover, the encapsulation of amorphous DL led to more disordered crystalline state of NLCs. In addition, in comparing the properties of NLCs and nanoemulsions (NEs) without CW, it was found that the addition of CW seemed to have several beneficial effects on NLCs: 1) NLC droplets were well dispersed, whereas NE droplets exhibited coalescence and flocculation; 2) compared with NEs, NLCs displayed excellent storage stability and inhibition ability of DL release. Furthermore, antifungal activity of NLCs was observed by in vitro and in vivo study. The acquired information in current research can provide novel insight into development of stable and antifungal nanocarriers that own a promising application in tomato preservation. [Display omitted] • NLCs were produced by pre-emulsification followed by ultrasonic treatment. • Candelilla wax (CW) was presumed to be important for the crystallization of NLCs. • CW endowed NLCs with high physical stability and retention rate of d -limonene. • NLCs showed good inhibition effect on the growth of Botrytis cinerea. [ABSTRACT FROM AUTHOR]

Psoriasis is a prevalent laborious inflammation in skin with alternate phases of remission and relapses. The current study sought to develop nanostructured lipid carriers (NLCs) having enhanced skin deposition as well as augmented anti-inflammatory potential, to repurpose the use of luteolin (Lut), a flavonoid, in the treatment of psoriasis. NLCs were prepared using different oils having reported anti-inflammatory activity and evaluated in terms of size, surface charge, entrapment efficiency, stability upon storage, in-vitro anti-inflammatory potential, surface morphology, in-vitro release profile and release kinetics, and ex-vivo skin deposition. In-vivo animal studies were conducted on the optimized formula using imiquimod-induced psoriasis rat model. The prepared NLCs were nanosized ranging from 202 to 538 nm, negatively charged with values having the range of -13.10 to -19.26 mV with high entrapment efficiency values ranging from 84.21 to 96.53% and high in-vitro anti-inflammatory potential compared to the blank and control formulations. Furthermore, NLCs demonstrated adequate storage stability demonstrated by slightly significant change in their colloidal properties. The prepared nanoparticles exhibited sustained drug release up to 24 h and succeeded in enhancing the skin deposition of Lut by 3.4-fold higher in stratum corneum, epidermis and dermis compared to Lut suspension with minimum transdermal delivery. In-vivo assessment of psoriasis was carried out morphologically, histopathologically and biochemically and results revealed significant augmentation of the anti-psoriatic efficacy of Lut upon its encapsulation in NLCs compared to free Lut suspension. The developed system proved to be an influential drug delivery system providing potent anti-psoriatic therapy, paving the way for futuristic clinical investigations. [Display omitted] [ABSTRACT FROM AUTHOR]

This work aims at (1) assessing the potential of repurposing simvastatin (SV) to support the most common therapies against melanoma and (2) developing an innovative topical adhesive film, composed by chitosan-coated nanostructured lipid carriers (Ch-NLC) used as drug vehicle. A factorial design approach was employed as the basis for the formulation development. Optimized Ch-NLC displayed a particle size of 108 ± 1 nm, a polydispersity index of 0.226, a zeta potential of 17.0 ± 0.6 mV, as well as an entrapment efficiency of 99.86 ± 0.08%, and SV loading of 14.99 ± 0.01%. The performance of SV-Ch-NLC films was assessed in terms of release, permeation, and adhesion, as critical quality attributes. Cutaneous tolerability and in vitro cytotoxicity studies were performed to warrant film safety and drug effectiveness, respectively. The topical films provided a sustained release kinetic profile of SV and were classified as nonirritant systems. The encapsulation of SV increased cytotoxicity in melanoma cells. The key role of squalene as nanostructuring agent of the lipid nanoparticle matrix and as permeation enhancer was highlighted, suggesting its key action for potentiating skin permeation and uptake into melanoma cells. Topical SV-Ch-NLC films are thus able to provide an in situ extended drug delivery and useful as coadjuvant treatment of melanoma skin lesions. [ABSTRACT FROM AUTHOR]

Intranasal nanostructured lipid carrier (NLC) of lurasidone hydrochloride (LRD) for brain delivery was prepared by the solvent evaporation method. The effects of independent variables, X1-lipid concentration, X-2 surfactant, and X-3 sonication times on dependent variables, Y1-particle size, Y-2 polydispersity index, and Y-3% entrapment efficiency were determined using Box-Behnken design. Optimized LRD-NLC was selected from the Box-Behnken design and evaluated for their morphological, physiological, nasal diffusion, and in vivo distribution in the brain after intranasal administration. Particle size, polydispersity index, and entrapment efficiency of optimized LRD-NLC were found to be 207.4 ± 1.5 nm, 0.392 ± 0.15, and 92.12 ± 1.0%, respectively. Transmission electron microscopy and scanning electron microscopy was used to determine the particle size and surface morphology of LRD-NLC. The prepared LRD-NLC follows biphasic in vitro drug release. Prepared NLC showed a 2-fold increase in LRD concentration in the brain when compared with the drug solution following intranasal administration. Results showed that intranasal route can be a good and efficient approach for delivering the drug directly to the brain and enhancing the drug efficacy in the brain for the management of schizophrenia and a good alternative to oral drug delivery. [ABSTRACT FROM AUTHOR]

• Doxorubicin and Sildenafil citrate were co-loaded in nanostructured lipid carriers. • Arginyl-glycyl-aspartic acid containing nanoparticles promote uptake of drugs. • Sildenafil citrate causes higher accumulation of Doxorubicin into cells. • Sildenafil citrate reduces expression of ABCC1 and Nrf2 in cancerous cells. Resistance to anticancer agents is considered as the main cause of chemotherapy failure. This study is aimed to prepare and optimize [Doxorubicin (Dox) + Sildenafil citrate (SC)]-coloaded Arginyl-glycyl-aspartic acid (RGD)-containing nanostructured lipid carriers (NLC-RGD) to overcome multidrug resistance limitation and improve cancer treatments. Consequently, [DOX + SC]-coloaded NLC-RGD were fabricated by homogenization method and characterized by several techniques. Then, cytotoxicity, cellular uptake, apoptosis, and expression level of some multi-drug resistance related genes were evaluated in [DOX + SC]-coloaded NLC-RGD treated cells. As results, particles with nano-size, narrow size distribution and suitable encapsulation efficiency (∼56% for DOX and ∼81% for SC) were prepared. Our Results also demonstrated that co-delivery of DOX and SC by NLC-RGD promotes uptake and accumulation of drugs by integrin mediated endocytosis and possible ABC transporter inhibition. Cytotoxicity and apoptosis experiments revealed that co-delivery of DOX and SC by NLC-RGD is more effective approach for induction of apoptosis in comparison to individual treatment and delivery. Gene expression experiments revealed that SC reduces expression of ABCC1 and Nrf2. These findings indicated that NLC-RGD can be considered as an appropriate delivery system for co-delivery of DOX and SC to overcome DOX resistance to improve treatment efficacy in cancer. [ABSTRACT FROM AUTHOR]

• Sophorolipid based NLCs are fabricated for the first time by hot dispersion method. • Highly innocuous nanovehicle developed for the delivery of rifampicin. • Large spherical nanostructures and smaller ellipsoidal micelles are present in NLCs. • There exists a strong interaction between rifampicin and bovine serum albumin. To date, the potential of sophorolipids (an important class of glycolipids) has been exploited solely as amphipathic molecules but their ability to formulate lipid nanoparticles has never been explored. In this report, for the first time, lipid nanostructures coated with polysorbates (Tweens) were formulated by a hot dispersion method. By varying the amount of lipid, type of surfactant, and alcohol, dilution ratio etc., the formulation was optimized with respect to its stability, which is a central aspect of their potential applications. Their comprehensive physicochemical characterization was done using static and dynamic light scattering (SLS, DLS), small angle neutron scattering (SANS), zeta-potential, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques. Further hemolysis study was conducted to understand the in-vitro cytotoxicity levels of the lipidic nanoparticles prior to its application as a potent drug delivery device for countermanding the problems associated with challenging tuberculosis and leprosy drug-Rifampicin. Attaining high entrapment efficiency and sustained release from the developed carrier, further interaction with bovine serum albumin was investigated, to understand the in-vivo behavior of the nanostructured lipid carriers (NLCs). [ABSTRACT FROM AUTHOR]

• Resveratrol loaded NLCs were systematically optimized employing QbD approach. • RSV-FA-NLCs depicted higher cytotoxic effects on MCF-7 cells compared to RSV-NLCs. • Drug loaded NLCs exhibited better pharmacokinetic parameters compared to free RSV. Resveratrol (RSV) has shown to possess anti-cancer potential in various studies; however, its poor water solubility, extensive first-pass metabolism, and photostability issues have limited its clinical application. Therefore, the aim of the current investigation was to formulate and optimize a nanostructured lipid carriers (NLCs) based parenteral formulation of RSV for its effective delivery to breast cancer cells. NLCs loaded with RSV (RSV-NLCs) were formulated by the modified solvent injection technique and were systematically optimized using a three level-three factor Box-Behnken design. The optimized RSV-NLCs exhibited an optimum particle size of 88.3 ± 3.1 nm and high entrapment efficiency of 88.0 ± 2.6%. These optimized NLCs were further investigated for the targeting potential using folic acid as the targeting moiety and cell cytotoxicity experiments revealed high cytotoxic effects of folate modified NLCs (RSV-FA-NLCs) compared to unmodified NLCs on MCF-7 cells with high levels of over-expressed folate receptors suggesting the high potential of targeted NLCs in enhancing the therapeutic concentration of RSV to breast cancer cells. In vivo pharmacokinetic studies demonstrated a nine-fold increase in AUC values obtained with RSV-FA-NLCs (57.92 ± 4.15 μg h/mLh) in comparison to free RSV (6.37 ± 1.16 μg h/mLh). The promising results from this investigation corroborated the tremendous potential of lipidic nanocarriers in augmenting the therapeutic potential of RSV. [ABSTRACT FROM AUTHOR]

• A new topical itraconazole nanocapsular gel was developed. • The gel is based on small monodisperse lipid nanocapsules (50 nm). • Lipid nanocapsules increased itraconazole antifungal activity and skin retention. • The itraconazole nanocapsular gel effectively cured cutaneous candidiasis in rats. • Lipid nanocapsules offer promise as itraconazole nanocarrier. There is a growing clinical demand for topical itraconazole (ITC) delivery systems because of the expanding potential of the drug for topical fungal and non-fungal applications. Lipid-based nanocarriers offer great promise in this respect. In the present study, a new topical ITC gel based on lipid nanocapsules (LNC) was developed. ITC-LNC were compared to ITC-loaded nanostructured lipid carriers (ITC-NLC) with more established benefits as topical vectors. Both nanocarriers showed high entrapment efficiency (EE > 98%). Compared to ITC-NLC, the ITC-LNC showed a significantly smaller particle size (∼50 vs 155 nm), narrower size distribution (0.09 vs 0.38), faster initial release rate under sink conditions and greater in vitro antifungal activity against Candida albicans (C. albicans) (inhibition zone 29.4 vs 26.4 mm). ITC-LNC and ITC-NLC-based gels significantly enhanced the dermal retention of ITC in excised human skin relative to a conventional ITC gel. Histopathological assessment of a 14-day treatment of induced cutaneous candidiasis in a rat model indicated efficacy of the gel preparations. Fungal elements developed in the superficial epidermal skin layer were cleared by the end of treatment. Equally important, no histopathological changes in the epidermal and dermal layers of rat skin were observed. Findings of this study verified efficacy of topical ITC in the treatment of superficial fungal infections as well as effectiveness of LNC as biomimetic nanocarrier for dermal drug delivery. Combining ITC and LNC would present a bioactive nanocarrier system with good potentials for fungal infections and other skin applications. [ABSTRACT FROM AUTHOR]

• Numerous studies have been conducted on phenytoin to promote the healing of ulcers. • Phenytoin is commercially available as a topical spray with high percentage of organic solvents that causes skin dryness, redness, irritation, burning and allergic contact dermatitis. • Hence, there is a need for new organic solvent-free topical formulations that can improve phenytoin wound healing ability with minimal or no adverse effects. • Nanostructured lipid carriers are advantageous in comparison to other topical carriers in several aspects with high percutaneous absorption due to their high surface area and negligible skin irritability. • Our aim is to develop a novel topical NLC for enhancing the entrapment efficiency and sustained release of phenytoin and study its impact on the healing of DFU in patients with no clinical evidence of ischaemia or infection. • PHT-NLC-dressing is more effective than PHT-hydrogel at the same concentration in healing of DFU. The aim of this study is to develop, and characterize nanostructured lipid carriers (NLCs) of phenytoin (PHT) in order to improve its entrapment efficiency and sustained release to improve the healing process. Twenty-seven patients with neuropathic diabetic foot ulceration (DFU) were enrolled in this study. Patients were comparable regarding size, grading of ulcer and control of diabetes with no major deformity. All patients were managed by weekly sharp debridement if indicated and offloaded with cast shoes. They were equally divided into three groups: PHT-NLC-hydrogel (0.5%w/v), phenytoin hydrogel (0.5%w/v) and blank hydrogel groups. Changes in wound area were monitored over 2 months. Baseline wound area of PHT-NLC, PHT and blank hydrogels were 5.50 ± 3.66, 3.94 ± 1.86 and 5.36 ± 2.14 cm2, respectively. Ulcers treated with PHT-NLC hydrogel showed smaller wound area compared to control groups (ρ < 0.05). The overall reduction in ulcer size were 95.82 ± 2.22% for PHT-NLC-hydrogel in comparison to 47.10 ± 4.23% and –34.91 ± 28.33% for PHT and blank-hydrogel (ρ < 0.001), respectively. PHT-NLC hydrogel speeds up the healing process of the DFU without adverse effects when compared to the positive and negative control hydrogels. Moreover, the study can open a window for topical application of NLCs loaded with PHT in the treatment of numerous dermatological disorders that resist conventional treatment. The delivery of drug molecules and their localization into the skin is the main purpose of the topical dosage forms. In this manuscript, the impact of topical phenytoin loaded nanostructured lipid carrier in improving wound healing in patients with neuropathic diabetic foot ulceration was investigated. Phenytoin loaded nanostructured lipid carrier dressing was found to be more effective than phenytoin hydrogel at the same concentration in healing of neuropathic diabetic foot ulcer. [ABSTRACT FROM AUTHOR]

Nanostructured lipid carriers (NLC) belong to youngest lipid-based nanocarrier class and they have gained increasing attention over the last ten years. NLCs are composed of a mixture of solid and liquid lipids, which solubilizes the active pharmaceutical ingredient, stabilized by a surfactant. The miscibility of the lipid excipients and structural changes (polymorphism) play an important role in the stability of the formulation and are not easily predicted in the early pharmaceutical development. Even when the excipients are macroscopically miscible, microscopic heterogeneities can result in phase separation during storage, which is only detected after several months of stability studies. In this sense, this work aimed to evaluate the miscibility and the presence of polymorphism in lipid mixtures containing synthetic (cetyl palmitate, Capryol 90®, Dhaykol 6040 LW®, Precirol ATO5® and myristyl myristate) and natural (beeswax, cocoa and shea butters, copaiba, sweet almond, sesame and coconut oils) excipients using Raman mapping and multivariate curve resolution – alternating least squares (MCR-ALS) method. The results were correlated to the macroscopic stability of the formulations. Chemical maps constructed for each excipient allowed the direct comparison among formulations, using standard deviation of the histograms and the Distributional Homogeneity Index (DHI). Lipid mixtures of cetyl palmitate/Capryol®; cetyl palmitate/Dhaykol®; myristyl myristate/Dhaykol® and myristyl myristate/coconut oil presented a single histogram distribution and were stable. The sample with Precirol®/Capryol® was not stable, although the histogram distribution was narrower than the samples with cetyl palmitate, indicating that miscibility was not the factor responsible for the instability. Structural changes before and after melting were identified for cocoa butter and shea butter, but not in the beeswax. Beeswax + copaiba oil sample was very homogenous, without polymorphism and stable over 6 months. Shea butter was also homogeneous and, in spite of the polymorphism, was stable. Formulations with cocoa butter presented a wider histogram distribution and were unstable. This paper showed that, besides the miscibility evaluation, Raman imaging could also identify the polymorphism of the lipids, two major issues in lipid-based formulation development that could help guide the developer understand the stability of the NLC formulations. Unlabelled Image [ABSTRACT FROM AUTHOR]

• Nanostructured lipid carriers (NLC) and nanoemulsions (NE) are safe for skin use. • Vitamin E-loaded NLC and NE demonstrate in vivo hydration potential. • Hydrogels containing NLC exhibited good skin occlusive properties. • Hydrogels containing NE performed a fast skin hydration effect. Lipid-based nanosystems, such as nanostructured lipid carriers (NLC) and nanoemulsions (NE) have been described as promising alternatives to conventional formulations for increase skin hydration. Besides, these systems have been used as efficient vehicles for lipophilic molecules that improve skin properties (e.g. vitamin E). In this study, we performed comparative investigations between hydrogels formulations containing vitamin E-loaded NLC (HG-NLC VE) and vitamin E-loaded nanoemulsion (HG-NE VE). The experiments started with particle size measurements, which showed no significant differences between nanoparticles/nanodroplets sizes after incorporation in the hydrogel net (386 nm vs. 397 nm for HG-NLC VE and 402 nm vs. 514 nm for HG-NE VE). Afterwards, in vitro biocompatibility studies in human keratinocytes were carried out, being observed that the lipid-based nanosystems were more cytotoxic for the cells before incorporation in the hydrogel. Finally, the formulations hydration potential and sensory attributes for skin application were evaluated by in vitro occlusion tests and in vivo human experiments. The results showed that the HG-NLC VE exhibited the best occlusive properties, whereas the HG-NE VE performed a faster skin hydration effect. Furthermore, the latter was selected as the most attractive for skin application, although the HG-NLC VE was described as more suitable to obtain a long-lasting effect. This study demonstrated the in vitro and in vivo safety and hydration potential of hydrogels containing vitamin E-loaded lipid-based nanosystems. These results establish a basis to assess the cutaneous use of these systems, despite more in vivo experiments, for longer periods and in more volunteers, are required before commercialization. [ABSTRACT FROM AUTHOR]

This research attempts to bring together the positive aspects of lipid nanoparticles and Quality by Design (QbD) approach for developing a novel drug delivery system for skin cancers and aktinic keratosis. Lipid nanoparticles which is one of the most efficacious options for topical treatment of skin diseases were prepared due to their ability to overcome the complex structure of skin barrier and to enhance the skin penetration. Since the formulation development contains complex variables of active ingredients, raw materials or production method; all the variables of the product should be elaborated. QbD approach which refers to design and develop formulations and manufacturing processes to maintain the prescribed product quality was also successfully adopted to achieve a time- and cost-saving process ensuring a high-quality product. 5-Fluorouracil (5-FU) loaded lipid nanoparticles, both solid lipid nanoparticles and nanostructured lipid carriers, were developed and characterized by following QbD steps. Optimal lipid nanoparticle formulation with guaranteed quality which was within the design space has been reached through the artificial neural networks. The optimal lipid nanoparticle formulation which is a NLC formulation with a mean particle size of 205,8 ± 9,34 nm, narrow size distribution (0.279 ± 0.01) and negative zeta potantial −30,20 ± 0,92 was produced by high pressure homogenization method. Cytotoxicity profiles of the optimal NLC was determined by cell culture studies on epidermoid carcinoma cells and human keratinocyte cells. Optimal NLC showed significantly higher anticancer effect on epidermoid carcinoma cells than free 5-FU and also less cytotoxicity towards human keratinocyte cells. Optimal NLC was formulated in hydrogel formulation for ease of application which has suitable occlusive and mechanical properties, viscocity and pH for patient complience. The cumulative amount of 5-FU in dermal tissues of rat skin was found 20.11 ± 2.14 μg/cm2 and 9.73 ± 0.87 μg/cm2 after application of NLC enriched hydrogel and 5-FU hydrogel respectively. In conclusion, this study showed that a time and cost saving process ensuring a high-quality product can be obtained by QbD guided formulation development study with the help of artificial neural networks. A novel semisolid dosage form enriched by NLC which is promising for topical treatment of skin cancers was developed. [ABSTRACT FROM AUTHOR]

Highlights • A novel combination of supramolecular solvents and nanostructured lipid carriers. • Astaxanthin from H. pluvialis powder is extracted, encapsulated and stabilized. • Spherical SUPRAS-NLCs of ∼100 nm were obtained. • Antioxidant and in vitro ROS scavenging properties are preserved and even enhanced. • A remarkable time stability of at least 180 d at 4 °C is guaranteed. Abstract The interest of food industry to merchandise natural astaxanthin is growing up. However, it confronts scientific and technological challenges mainly related to its poor water solubility and chemical instability. Here, we present a new quick and efficient green process to simultaneously extract, encapsulate and stabilize astaxanthin from Haematococcus pluvialis. The process is based on the hitherto unexplored combination of supramolecular solvents (SUPRAS), nanostructured liquids generated from amphiphiles through sequential self-assembly and coacervation, and nanostructured lipid carriers (NLCs). These novel nanosystems were characterized by means of dynamic light scattering, AFM and cryoSEM, revealing spherical particles of ∼100 nm. Their antioxidant activity was measured by ORAC (20.6 ± 3.9 μM TE) and α-TEAC (2.92 ± 0.58 µM α-TE) assays and their in vitro capacity to inhibit ROS by DHE probe. Results showed that the SUPRAS-NLCs proposed yield high extraction and encapsulation efficiencies (71 ± 4%) in combination with a remarkable time stability (180 d, 4 °C). [ABSTRACT FROM AUTHOR]

Abstract This study investigated spray drying of food-grade solid lipid particles (SLN) and nanostructured lipid carriers (NLC) containing ω-3 fish oil. Stable SLN and NLC dispersions with tristearin as carrier lipid were formed by using a combination of Quillaja saponins and high-melting lecithin as emulsifiers. Our specific goal was to study the influence of four different spray drying inlet and outlet temperatures (T inlet/outlet = 140–170 °C/65–95 °C) and two different maltodextrin types (DE 6 and DE 21) with different molecular weights as protective wall materials on the physical and polymorphic stability of the solid lipid particles. The results revealed that the low molecular weight maltodextrin DE 21 was a superior wall material in stabilizing the solid lipid particles. Moreover, the lipid particles spray dried at T inlet/outlet of 140/65 °C exhibited the highest physical and polymorphic stability, whereas using higher T inlet/outlet led to bigger particles which were more prone to polymorphic transition. This was also verified in a 71-day storage test. The findings were explained that by preventing the melting of the tristearin carrier lipid during spray drying, the crystallized lipid particles remained intact inside the amorphous maltodextrin layer and exhibited high physical and polymorphic stability. These findings are important for generating stable food-grade spray dried powders. Graphical abstract Unlabelled Image Highlights • Spray drying of food-grade solid lipid particles was investigated. • Impact of inlet temperature and wall material type upon spray drying was studied. • Low molecular weight maltodextrin was better in stabilizing the solid lipid particles. • The highest physical and polymorphic stability was achieved at T inlet of 140 °C. [ABSTRACT FROM AUTHOR]

Both phosphodiesterase (PDE4) inhibitors and omega-9 fatty acids show anti-inflammatory activity for treating inflamed skin diseases, but their efficacy remains low. Combinatorial agents are anticipated to offer an advanced strategy for efficient therapy. We prepared cilomilast-loaded oleic acid (OA) nanocarriers to test the inhibitory capability against human neutrophil stimulation and a murine psoriasis model. OA played dual roles in the nanocarriers as both the active ingredient and lipid matrix in the nanoparticulate core. OA nanoparticles but not free OA could restrain calcium mobilization in activated neutrophils. The inhibition level of superoxide anion and elastase by cilomilast-loaded OA nanocarriers approximated that of free forms. In the mouse model, the intradermal nanosystems reduced imiquimod-induced epidermal thickening from 230.4 to 63.1 μm. Transepidermal water loss was decreased from 30.2 to 11.3 g/m2/h by integrated nanocarriers. The nanosystems mitigated neutrophil infiltration and hyperproliferation in the psoriasiform lesion via decreased expression of cytokines and chemokines. The long-term therapy for psoriasis is unsatisfactory due to the possible adverse effects and inefficiency after prolonged use. Both phosphodiesterase (PDE4) inhibitors and omega-9 fatty acids such as oleic acid (OA) show anti-inflammatory activity for treating inflamed skin diseases. Combinatorial agents are anticipated to offer an advanced strategy for efficient therapy. OA is also ideal for incorporation into nanoparticles to enhance particulate emulsification, drug entrapment, and biocompatibility. We prepared cilomilast-loaded oleic acid (OA) nanocarriers to test the inhibitory capability against human neutrophil stimulation and a murine psoriasis lesion. OA nanocarriers are indigenous to prevent neutrophil activation and the deterioration of psoriatic lesion. Cilomilast incorporation in OA nanocarriers could further mitigate the clinical score and suppressing proinflammatory mediators. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Smaller NR-NLC-40 showed greater transcorneal penetration than the larger ones. • Both PEG-coated and positively charged particles improved the ocular mucoadhesive property of NLCs. • Negatively charged NLCs revealed higher PCE cell uptake than the PEG coated and positively charged ones. • Negatively charged uncoated NLCs can be useful for lipophilic drug delivery to the anterior segment. • PEG-coated and positively charged NLCs could be potentially used to treat ocular surface disorders. Abstract Nile Red-loaded nanostructured lipid carriers (NR-NLCs), prepared by high-pressure homogenization technique, have been investigated for their transcorneal penetration using a confocal scanning microfluorometer (CSMF). Topical exposure of NR-NLCs led to their penetration into the epithelium and anterior stroma. The NR-NLC-40 (NR-NLCs of 40 nm) showed faster penetration compared to NR-NLC-150 (NR-NLCs of 150 nm). The surface modification of NR-NLC-40 with polyethylene glycol 400 (NR-NLC-PEG) and stearylamine (NR-NLC-SA), although did not cause any significant effect on size, resulted in an increased penetration into the epithelium concomitant with a reduced penetration into the stroma compared to the NR-NLC-40. Ex vivo mucoadhesion assay revealed that NR-NLC-PEG and NR-NLC-SA adhered more strongly to the porcine corneal surface compared to NR-NLC-40. Flow cytometry experiments with porcine corneal epithelial cells showed that NR-NLC-40 was internalized better than NR-NLC-PEG and NR-NLC-SA. These results, taken together, suggest that NLCs are potentially useful for lipophilic drug delivery to the corneal epithelium and anterior stroma without any surface modifications. However, surface modifications with polyethylene glycol 400 or stearylamine could be useful to treat ocular surface disorders. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • LCN F is an alternative to overcome fluconazole fungal resistance in Candida. • LNC F was effective against resistant strains that have active efflux pump mechanism. • Nanopaticles-fluconazole caused morphological changes in the cell wall of Candida. • Supramolecular structure and nanoparticles composition impact on antifungal action. • Potential application in the medical treatment of resistant fungal infections. Abstract Fungal resistance is the major problem related to fluconazole treatments. This study aims to develop innovative lipid core nanocapsules and nanostructured lipid carriers containing fluconazole, to study in vitro antifungal activity and to assess the possibility of resistance reversion in Candida albicans , C. glabrata , C. krusei, and C. tropicalis isolates. The action mechanism of nanoparticles was investigated through efflux pumps and scanning electron microscopy studies. The lipid core nanocapsules and nanostructured lipid carriers were prepared by interfacial deposition of preformed polymer and high-pressure homogenization methods, respectively. Both nanostructures presented sizes below 250 nm, SPAN < 1.6, negative zeta potential, pH slightly acid, high drug content and controlled drug release. The nanostructured lipid carriers were unable to reverse the fungal resistance. Lipid core nanoparticles displayed advantages such as a reduction in the effective dose of fluconazole and resistance reversion in all isolates tested - with multiple mechanisms of resistance. The main role of the supramolecular structure and the composition of the nanoparticles on antifungal mechanisms of action were discussed. The results achieved through this study have an impact on clinical therapy, with a potential application in the treatment of fungal infections caused by resistant isolates of Candida spp. [ABSTRACT FROM AUTHOR]