Tailored green synthesized silymarin-selenium nanoparticles: Topical nanocarrier of promising antileishmanial activity.

Poor drug penetration, emerging drug resistance, and systemic toxicity are among the major obstacles challenging the current treatment of cutaneous leishmaniasis. Hence, developing advanced strategies for effective and targeted delivery of antileishmanial agents is crucial. Several drug delivery carriers have been developed till current date for dermal/transdermal delivery, especially those which are fabricated using eco-friendly synthesis approaches, since they protect the environment from the harmful effects of chemical waste disposal. This work describes the preparation of selenium nanoparticles loaded with silymarin via one-pot green reduction technique, for treatment of cutaneous leishmaniasis. The selected silymarin loaded selenium nanoparticles (SSNs4-0.1) displayed good loading efficiency of 58.22 ± 0.56 %, zeta potential of -30.63 ± 0.40 mV, hydrodynamic diameter of 245.77 ± 11.12 nm, and polydispersity index of 0.19 ± 0.01. It exhibited good physical stability, as well as high ex vivo deposition % in the epidermis (46.98 ± 1.51 %) and dermis (35.23 ± 1.72 %), which was further proven using confocal laser microscopy. It also exhibited significant cytocompatibility and noticeable cellular internalization of 90.02 ± 3.81 % in human fibroblasts, as well as high trypanothione reductase inhibitory effect (97.10 ± 0.30 %). Results of this study confirmed the successful green synthesis of silymarin-loaded selenium nanoparticles; delineating them as one of the promising antileishmanial topical delivery systems.

Simplex Lattice Design and Machine Learning Methods for the Optimization of Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability: In Vitro and In Vivo Studies.

Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared. The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time. The loaded formulae were significantly more cytotoxic on all cell lines by 11.98-16.56 folds on MCF-7 and CaCo2 cells and 47.82-98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5-1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer.

Developing a rapid analytical method for simultaneous determination of apigenin and gallic acid: validation and application in a nanoliposomal formulation.

OBJECTIVE: Apigenin and gallic acid are natural compounds that are useful as antioxidant, anti-inflammatory and anticancer agents, especially when used together in combination. Therefore, the development and validation of a simultaneous method of analysis for both compounds in pure form and when encapsulated in an advanced delivery system such as liposomes would be useful. METHODS: Analysis was performed using C18 column under isocratic conditions. The mobile phase was acetonitrile: water containing 0.2% orthophosphoric acid at a ratio of 67:33, flow rate 1 ml/min, and detection wavelength 334 nm for apigenin and 271 nm for gallic acid. RESULTS: The assay method was linear at the concentration range (5-600 µg/mL) with R2 of 1 for both drugs. The method was also shown to be precise and robust with RSD less than 2% with LOD (0.12, 0.1 µg/mL) and LOQ (4.14, 3.58 µg/mL) for apigenin and gallic acid respectively. The method was also applicable for the determination of the entrapment efficiency of both drugs when co-loaded in a nanoliposomal formulation. CONCLUSION: The described HPLC method was shown to be suitable, sensitive, and reproducible for the simultaneous identification and quantification of apigenin and gallic acid. The analytical results were accurate and precise, with good recovery, low limit of detection, and the chromatographic assay was accomplished in less than 3 min, suggesting the suitability of the method for routine analysis of both drugs in pharmaceutical formulations.

Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality.

Ischemic stroke accounts for about 87% of all strokes, causing long-term disability in adults, and is the second leading cause of death worldwide. In search of new therapeutic modalities, the use of neuroprotective agents loaded in nanocarriers to be delivered by noninvasive means (i.e. via intranasal route) became a popular approach. In the current study, melatonin (MEL) was loaded in lipidic nanocapsules (LNCs) prepared using the phase inversion method, and characterized in terms of size, polydispersity, zeta potential, in vitro drug release, viscosity, storage stability, and ex vivo permeation across sheep nasal mucosa. Moreover, MEL-LNCs were tested for efficacy in cerebral ischemia/reperfusion (I/R/) injury model through histopathological assessment, and analysis of oxidative stress markers, pro-inflammatory cytokines, and apoptotic markers. Results showed that LNCs exhibited particle size ranging from 18.26 to 109.8 nm, negative zeta potential, good storage stability, spherical morphology, and a burst release followed by a sustained release pattern. LNCs exhibited 10.35 folds higher permeation of MEL than the drug solution across sheep nasal mucosa. Post-ischemic intranasal administration of MEL-LNCs revealed lowering of oxidative stress manifested by a decrease in malondialdehyde levels, and elevation of glutathione and superoxide dismutase levels, lowering of the inflammatory markers tumor necrosis factor-α, NO, myeloperoxidase, and significant inhibition of Caspase-3 activity as an apoptotic marker. Western blot analysis delineated a recovery of protein expression Nrf-2 and HO-1 with downregulation in the parent inflammatory markers nuclear factor kappa B p65, inducible nitric oxide synthase, Bax, and Cytochrome C expressions, and upregulation of B-cell lymphoma-2 Bcl-2, hence promoting neuronal survival. This was supported by histological evidence, revealing significant restoration of hippocampal neurons. In light of the above, it can be concluded that MEL-LNCs could be a promising delivery system for nose to brain delivery for treatment of cerebral ischemia.

Intranasally administered melatonin core-shell polymeric nanocapsules: A promising treatment modality for cerebral ischemia.

AIMS: The neurohormone melatonin (MEL) has been reported as a promising neuroprotective molecule, however it suffers pharmaceutical limitations such as poor solubility and low bioavailability, which hinder its pharmacological and clinical potential. In the current work, MEL was loaded in core-shell nanocarrier system; polymeric nanocapsules (PNCs), and assessed for its potential in cerebral ischemia reperfusion injury rat model when administered intranasally. KEY FINDINGS: Adopting a D-optimal factorial design, MEL-PNCs were successfully formulated using the nanoprecipitation technique. MEL-PNCs exhibited a particle size ranging from 143.5 to 444 nm, negative zeta potential values ranging from -24.2 to -38.7 mV, cumulative release % for MEL ranging from 36.79 to 41.31 % over 8 h period, with overall good storage properties. The selected MEL-PNCs formulation displayed 8-fold higher permeation than the drug solution across sheep nasal mucosa. MEL-PNCs administered intranasally decreased oxidative stress and hippocampal inflammation, and the histological examination revealed the significant restoration of hippocampal neurons. SIGNIFICANCE: MEL-PNCs administered intranasally could be a promising treatment modality in brain ischemia.

Simultaneous pulmonary administration of celecoxib and naringin using a nebulization-friendly nanoemulsion: A device-targeted delivery for treatment of lung cancer.

BACKGROUND: Lung cancer is a principal cause of death worldwide, and its treatment is very challenging. Nebulization offers a promising means of targeting drugs to their site of action in the lung. RESEARCH DESIGN AND METHODS: In the present study, nebulizable oil in water nanoemulsion formulations was co-loaded with naringin/celecoxib and tested for pulmonary administration by different nebulizer types. RESULTS: The translucent appearance of nanoemulsion formulations was revealed, with particle size (75-106 nm), zeta potential (-3.42 to -4.86 mV), and controlled in-vitro release profiles for both drugs. The nanoemulsions showed favorable stability profiles and superior cytotoxicity on A549 lung cancer cells. Aerosolization studies on the selected nanoemulsion formulation revealed its high stability during nebulization, with the generation of an aerosol of small volume median diameter and mass median aerodynamic diameter lower than 5 µm. Moreover, it demonstrated considerable safety and bioaccumulation in lung tissues, in addition to accumulation in the brain, liver, and bones, which are the main organs to which lung cancer metastasizes. CONCLUSIONS: Nanoemulsion proved to be a promising nebulizable system, which paves the way for treatment of pulmonary diseases other than lung cancer.

Quercetin loaded cosm-nutraceutical electrospun composite nanofibers for acne alleviation: Preparation, characterization and experimental clinical appraisal.

In the cosmeceutical field, it is essential to develop topical delivery systems which would allow drugs to create a depot and permeate within the skin. The aim of the present study was to develop composite nanofibers of polyvinyl alcohol/quercetin/essential oils using the electrospinning technique, and assess their efficiency in acne alleviation. Quercetin was chosen due to its anti-inflammatory, anti-oxidant, and antibacterial activities. Nanofibers were characterized for their morphology, ex-vivo deposition/permeation, physical/mechanical integrity, thermal properties, and chemical characteristics. In addition, the anti-bacterial efficacy was tested on Propionibacterium acne (P. acne), and a cytotoxicity assay was carried out. Lastly, an experimental clinical trial was conducted on acne patients, where the percentage reduction of inflammatory, non-inflammatory and total acne lesions was taken as evaluation criterion. Results showed that quercetin was successfully loaded into the nanofibers which were homogenously dispersed. They showed a reasonable skin deposition percentage of 28.24% ± 0.012, a significantly higher antibacterial efficacy against Propionibacterium acne than quercetin alone, and were utterly safe on skin fibroblastic cells. Upon clinical examination on acne patients, the nanofibers showed 61.2%, 14.7%, and 52.9% reduction of inflammatory, comedonal, and total acne lesions respectively, suggesting a promising topical anti-acne delivery system.

Nobiletin-loaded composite penetration enhancer vesicles restore the normal miRNA expression and the chief defence antioxidant levels in skin cancer.

Skin cancer is one of the most dangerous diseases, leading to massive losses and high death rates worldwide. Topical delivery of nutraceuticals is considered a suitable approach for efficient and safe treatment of skin cancer. Nobiletin; a flavone occurring in citrus fruits has been reported to inhibit proliferation of carcinogenesis since 1990s, is a promising candidate in this regard. Nobiletin was loaded in various vesicular systems to improve its cytotoxicity against skin cancer. Vesicles were prepared using the thin film hydration method, and characterized for particle size, zeta potential, entrapment efficiency, TEM, ex-vivo skin deposition and physical stability. Nobiletin-loaded composite penetration enhancer vesicles (PEVs) and composite transfersomes exhibited particle size 126.70 ± 11.80 nm, 110.10 ± 0.90 nm, zeta potential + 6.10 ± 0.40 mV, + 9.80 ± 2.60 mV, entrapment efficiency 93.50% ± 3.60, 95.60% ± 1.50 and total skin deposition 95.30% ± 3.40, 100.00% ± 2.80, respectively. These formulations were selected for cytotoxicity study on epidermoid carcinoma cell line (A431). Nobiletin-loaded composite PEVs displayed the lowest IC50 value, thus was selected for the in vivo study, where it restored skin condition in DMBA induced skin carcinogenesis mice, as delineated by histological and immuno-histochemical analysis, biochemical assessment of skin oxidative stress biomarkers, in addition to miRNA21 and miRNA29A. The outcomes confirmed that nobiletin- loaded composite PEVs is an efficient delivery system combating skin cancer.

Chrysin nanocapsules with dual anti-glycemic and anti-hyperlipidemic effects: Chemometric optimization, physicochemical characterization and pharmacodynamic assessment.

Chrysin is a flavonoid with various biological and therapeutic properties. However, its poor oral bioavailability and solubility are challenging barriers against its therapeutic use, which can be circumvented via encapsulation in a suitable nanocarrier. Therefore, the aim of this work was to prepare polymeric chrysin nanocapsules based on polylactic-glycolic acid PLGA with improved oral therapeutic potential, by optimization of their physicochemical properties using response surface methodology. Diabetes was induced in an animal model using streptozotocin to assess the anti-hyperglycemic activity of the selected formulation, and hyperlipidemia was induced in another animal model using a high fat diet to assess its anti-hyperlipidemic activity. Results revealed that the selected chrysin nanocapsular formulation exhibited particle size of 176 ± 2.10 nm, polydispersity index of 0.22 ± 0.01, negative zeta potential, drug entrapment efficiency of 87.10% ± 6.71, a controlled release of chrysin over a period of 24 h, and a significant physical stability after storage for 3 months. Compared to chrysin suspension, the selected nanocapsular formulation exhibited marked anti-hyperglycemic effect for up to 24 h, as well as superior anti-hyperlipidemic potential for 28 days. These improvements in chrysin therapeutic action after its encapsulation into polymeric nanocapsules delineate it as a promising remedy for oral treatment of diabetes and hyperlipidemia.

Bergamot oil as an integral component of nanostructured lipid carriers and a photosensitizer for photodynamic treatment of vitiligo: Characterization and clinical experimentation.

Background: Bergamot oil (BO) is a photosensitizer that can be used for photodynamic therapy (PDT) of dermatological diseases such as vitiligo. Being an oil, it can be integrated within the lipidic matrix of nanostructured lipid carriers (NLCs) as the liquid lipid constituent, hence exhibiting a dual role. Research design and methods: NLCs were prepared with different emulsifiers and coemulsifiers, and the effect of the preparation method and formulation variables on the NLCs' size was elucidated. The prepared NLCs were further characterized for their in vitro release, viscosity, thermal behavior, and in vitro photostability. Furthermore, a preclinical photodynamic study on animal skin was conducted, followed by clinical experimentation on patients with vitiligo. Results: Results showed that BO was successfully incorporated within the NLCs. The selected NLCs formulation was in the nanometer range with a gel consistency, and it provided sustained release of BO for 24 h. NLCs improved the photostability and photodynamic properties of BO, and displayed promising preclinical and clinical results for the topical PDT of vitiligo. Expert Opinion: BO containing NLCs was proven to be promising means for PDT of vitiligo, and can be further explored in other dermatological diseases.

Enhancement of oral bioavailability of drugs using lipid-based carriers: a meta-analysis study.

Cancer is the disease of this era. Its therapy is moving through ups and downs not only due to poor effectiveness of many treating drugs, but also due to the serious side effects always evolving. In an attempt to overcome this problem, many systems, including lipid-based carriers, have been exploited for their oral delivery. Throughout this study, the meta-analysis tool was used to combine data from different studies and extract evidences that lipid-based carriers enhance the oral bioavailability. Consequently, increasing the efficiency and the reduction in side effects of drugs would follow. Accordingly, the usual parameter to indicate the bioavailability; the area under effect curve (AUC) was used where the lipid carriers have proven their superiority over conventional formulations. Interestingly, by comparing microemulsion/self-microemulsifying system (SMEDDS) versus liposomes/pro-liposomes as subgroups of the meta-analysis study, insignificant differences were recorded between them.

Fabrication of extended-dissolution divalproex tablets: a green solvent-free granulation technique.

Objective: Divalproex sodium (DVS) is a challenging drug owing to its hygroscopicity, bitter taste, and short in vivo half-life. This study aims to produce stable taste masked DVS once daily tablets using solvent free hot melt granulation (HMG) process.Methods: A lab scale high shear mixer granulator employing six meltable lipid binders (compritol®888 ATO, beeswax, gelucire®50/13, precirol® ATO5, stearyl alcohol, and geleol®) was used for the preparation of tablets. Quality control tests were performed on granules and tablets, and Box-Behnken's design was adopted to investigate the effect of binder concentration, impeller speed, and granulation time on the drug dissolution. Shelf and accelerated stability evaluation, taste assessment, and in vivo pharmacokinetic study were conducted on the selected batches.Results: Results revealed that DVS tablets were successfully prepared, and that the in vitro dissolution of the drug was inversely proportional to the binder concentration. Beeswax and compritol® tablets showed similar dissolution profiles to the marketed product Depakote® 500 ER tablets (F1 < 15 and F2 > 50). The selected batches showed lower moisture content (<2%) and successfully masked the bitter taste compared to uncoated tablets based on a hydrophilic matrix. The in vivo pharmacokinetic study delineated relative bioavailability values for Beeswax and Compritol® tablets of 95.6% and 118%, respectively, compared to the marketed product.Conclusion: The solvent free HMG process can be employed to formulate 24 h extended dissolution DVS tablets with masked bitter taste and high stability, and comparable or higher bioavailability than the marketed product.

Nanoemulsion as a feasible and biocompatible carrier for ocular delivery of travoprost: Improved pharmacokinetic/pharmacodynamic properties.

Travoprost is a synthetic prostaglandin F2α analogue used in treatment of glaucoma. Due to its water insolubility and oily nature, novel delivery systems need to be developed to enhance its bioavailability, and sustain its release. In the current work, travoprost nanoemulsion was explored as a novel carrier prepared using low energy technique. Results showed that travoprost nanoemulsions exhibited suitable nanodroplet size, zeta potential, pH, refractive index, controlled release, as well as sufficient stability under accelerated conditions. In vivo studies delineated the enhanced absorption of travoprost nanoemulsion compared to the marketed eye drops Travatan®, as proven by the higher Cmax and AUC of the former, and its prolonged intraocular pressure reduction time. Moreover, the nanoemulsion formulation was proven safe and non-irritant to ocular surfaces. Therefore, it can be suggested that travoprost nanoemulsion is a promising ocular delivery system for glaucoma treatment.

Cosm-nutraceutical nanovesicles for acne treatment: Physicochemical characterization and exploratory clinical experimentation.

The full exploration of the 'nutraceuticals' therapeutic potential in cosmetics has been hindered by their poor stratum corneum permeation. Therefore, the aim of the present study was to formulate a nutraceutical; quercetin, in novel vitamin C based nanovesicles (aspasomes), and to explore their beneficial effects in the treatment of acne. Aspasomes were characterized for their particle size, zeta potential, entrapment efficiency (EE%), 3-months storage stability, skin deposition/permeation, antioxidant potential, and morphology. Aspasomes antibacterial efficacy on Propionibacterium acnes using the zone of inhibition assay was also tested, whilst their safety on skin fibroblastic cells was assessed in vitro using 3T3 CCL92 cell lines. An exploratory clinical trial was conducted in acne patients, and the percentage reduction of inflammatory, non-inflammatory and total acne lesions was taken as the evaluation criterion. Results revealed that quercetin-loaded aspasomes displayed a desirable nanometer size (125-184 nm), negative charge with good storage stability, and high skin deposition reaching 40%. Aspasomes managed to preserve the antioxidant activity of quercetin, and exhibited a significantly higher antibacterial effect (15 ± 1.53 mm) against Propionibacterium acnes than quercetin alone (8.25 ± 2.08 mm), and were safe on skin fibroblastic cells. Upon clinical examination in 20 acne patients (14 females, 6 males), quercetin aspasomes exhibited reduction percentages of 77.9%, 11.8% and 55.3% for inflammatory lesions, comedones and total lesions respectively. This opens vast applications of the presented formulation in the treatment of other oxidative skin diseases, and delineates the nutraceuticals and nanoformulations prepared from natural materials as promising dermatological treatment modes.

Pharmacokinetic/pulmokinetic analysis of optimized lung targeted spray dried ketotifen-dextran core shell nanocomplexes-in-microparticles.

A passive lung targeted system for controlled lung delivery of ketotifen (KT) was developed based on the green complexation of dextran sulphate (DS) and KT. Achieving deep lung deposition of high drug fraction, while evading lung defense mechanisms were set as goals. Optimized uniform negatively charged nanocomplexes (NC), <80 nm, were obtained at KT/DS weight ratio of 1:0.66 to 1:0.5 and 1% surfactant concentration with 90% drug complexation efficiency. The interaction between KT and DS and matrix formation were evidenced by Fourier-transform infrared (FT-IR) spectra and differential scanning calorimetry (DSC) studies. A respirable particle percent reaching 67.41 ±â€¯2.6% was obtained following co-spray drying NC containing poloxamer with leucine. A higher lung/plasma partitioning was obtained following pulmonary administration of selected nanocomplexes in microparticles (NCEMP) to rats compared to oral and intravenous (iv) routes. A new core shell nanocomplex formed of DS and KT as main substrates exhibited a potential for lung targeting of the anti-asthmatic drug.

Novel bergamot oil nanospanlastics combined with PUVB therapy as a clinically translatable approach for vitiligo treatment.

The impact of nanomedicine has grown in the current decade; however, only very few clinical translational attempts have been realized. Therefore in the present study, we hypothesized that bergamot oil, a psoralen-containing oil, would produce an optimized melanogenic effect in the clinical treatment of vitiligo when loaded within an elastic nanocarrier (spanlastics) and combined with PUVB for activation of psoralens. Spanlastics were prepared and characterized for particle size, physical stability, in vitro release, thermal behavior, deformability, morphology, and in vitro photostability. The efficacy of the selected formula was tested histopathologically on rat skin and clinically translated in patients suffering from vitiligo. Results revealed that the spanlastics were of reasonable nanosize, deformable, and provided sustained release of bergamot oil. The incorporation of bergamot oil within spanlastics improved its photostability and its photodynamic activity. Spanlastics exhibited promising clinical results in terms of extent and onset of repigmentation in vitiligo patients. Therefore, it can be concluded that spanlastics can be introduced as a promising nanotreatment modality for vitiligo.

Optimisation of the microencapsulation of lavender oil by spray drying.

Background: Lavender oil consists of around 100 components and is susceptible to volatilisation and degradation reactions. Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated. Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography-mass spectrometry. Results: Lavender microparticles of size 12.42 ± 1.79 µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12 mg w/w%), and encapsulation efficiency (77.89 w/w%). Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend.

Insights on the Use of Nanocarriers for Acne Alleviation.

Among the common myths in the cosmetics industry is the perception that acne only happens to teenagers, and specifically to females. However, acne is neither limited to a specific age, nor to a certain gender, it creates a stressful problem for many people. Many chemical treatments for acne were proven to be successful, but when administered as such, they showed many adverse effects, starting from itching to skin dryness and inflammation. Natural remedies have also been explored for acne treatment, and despite their safety, they suffered many stability problems attributed to their physicochemical properties, creating an obstacle for their topical delivery. Therefore, many nanocarriers were used to deliver those chemical and natural remedies topically to maximize their therapeutic potential in acne treatment. The present review discusses the different nanocarriers which were proven successful in improving the acne lesions, focusing on vesicular, lipidic, and polymeric systems.

Curcumin-loaded ultradeformable nanovesicles as a potential delivery system for breast cancer therapy.

In the current study, the transdermal route has been investigated to deliver the poorly bioavailable drug; curcumin into the systemic circulation, aiming to target both superficial and subcutaneous tumors such as the breast tumors. Accordingly, different colloidal carriers viz. ultradeformable nanovesicles comprising various penetration enhancers were exploited. Curcumin-loaded deformable vesicles were prepared by the thin film hydration method followed by extrusion. Sodium cholate and Tween 80 were set as standard edge activators and Labrasol, Transcutol, limonene and oleic acid were the penetration enhancers that were evaluated for their efficacy in skin permeation. The particle size and zeta potential of the prepared vesicles were significantly affected by the type of surfactant/penetration enhancer. The polydispersity measurements showed uniform particle size distribution indicating the sufficiency of the extrusion cycles performed. Curcumin, as a hydrophobic molecule, was well accommodated within the lipid bilayers of the prepared vesicles with entrapment efficiency (EE%) percentages and drug loading percentages (DL%) as high as 93.91% and 7.04%, respectively. The ex-vivo permeation studies were performed on male albino mice skin mounted on Franz diffusion cells. Oleic acid and Transcutol exhibited comparable fluxes to sodium cholate and Tween 80 (∼16 µg cm-2 h-1), whereas the fluxes of Labrasol and limonene were significantly lower. Cytotoxicity studies were performed using MTT assay on human breast cancer cell lines (MCF-7 cells). The results of the MTT assay demonstrated that oleic acid ultradeformable nanovesicles scored an IC50 of 20 µg/ml which introduce these new curcumin-loaded nanovesicles as a successful delivery system for breast cancer therapy.

In vitro stabilization and in vivo improvement of ocular pharmacokinetics of the multi-therapeutic agent baicalin: Delineating the most suitable vesicular systems.

Baicalin is a multi-purpose flavonoid used in the treatment of different ocular diseases. Owing to its poor stability in basic pH and its poor solubility, a suitable carrier system is needed to enhance its ocular therapeutic potential. Therefore, the objective of this work was to prepare and contrast different baicalin vesicular systems; namely liposomes, penetration enhancer vesicles PEVs and transfersomes. Results revealed that baicalin vesicles exhibited suitable particle size and zeta potential, high entrapment efficiency and controlled release. Depending on the vesicular composition, selected formulations were able to resist physical changes of particle size, zeta potential, entrapment efficiency and in vitro release after storage for 3 months, while retarding the degradation of baicalin. Selected vesicular formulations displayed equivalent or superior antioxidant potential compared to baicalin solution, with absolute superiority over ascorbic acid reference, while demonstrating sterilization endurance and safety on ocular tissues. Pharmacokinetic studies revealed that transfersomes displayed the fastest onset of action, while liposomes displayed the highest extent of absorption as concluded from the Tmax, Cmax, and AUC0-∞ values with 4-5 folds increase in bioavailability compared to baicalin control solution. This delineates baicalin vesicular systems as a promising platform for treatment of ocular diseases such as inflammation, cataract and diabetic retinopathy.