Formulation and In-vitro Characterization of Metformin Hydrochloride-loaded Liposomes

The aim of study. is to formulate Metformin hydrochloride-loaded novel liposomal vesicles and investigate their physical stability. A new metformin hydrochloride (Met-HCL) liposomal formulation was prepared  for topical delivery. Traditionally, the biguanide metformin could be categorized the first line in treatment of diabetes. The prepared metformin hydrochloride-loaded liposomal vesicles were investigated  for different in vitro characterisations. Eleven different formulations were developed adopting a thin film hydration method using different molar concentrations of Phospholipon® 90G, cholesterol and metformin hydrochloride. The effect of varying concentrations of Phospholipon® 90G, cholesterol and metformin hydrochloride on entrapment efficiency percent, ex-vivo skin permeation percentage, vesicle size and zeta potential was studied. Metformin-loaded liposome stability over a period of time 90 days was investigated. Results. The optimized metformin hydrochloride liposomes, F2, F6 and F11 were selecte. The selected formulations displayed highly efficient permeation percent via the excised mice skin 53±0.09 %, 30±0.4 % and 40±0.02 % respectively. The formulations showed EE % of  80±0.09 %, 28.6±0.02 % and 71.8±0.4 % respectively. Morphology of F2  liposomal surface revealed spherical three-dimensional structure. The stability study revealed about 10-23 percent drug leaching out of the vesicular liposomes (F2) within 90 days. Conclusion. Metformin hydrochloride-loaded liposomal vesicles can provide a potentially promising and convenient approach for topical delivery

Hybrid thermosensitive-mucoadhesive 'in situ' forming gels for enhanced corneal wound healing effect of L-carnosine

PURPOSE: Thermosensitive in situ gels have been around for decades but only a few have been translated into ophthalmic pharmaceuticals. The aim of this study was to combine the thermo-gelling polymer poloxamer 407 and mucoadhesive polymers chitosan (CS) and methyl cellulose (MC) for developing effective and long-acting ophthalmic delivery systems for L-carnosine (a natural dipeptide drug) for corneal wound healing. METHODS: The effect of different polymer combinations on parameters like gelation time and temperature, rheological properties, texture, spreading coefficients, mucoadhesion, conjunctival irritation potential, in vitro release, and ex vivo permeation were studied. Healing of corneal epithelium ulcers was investigated in a rabbit’s eye model. RESULTS: Both gelation time and temperature were significantly dependent on the concentrations of poloxamer 407 and additive polymers (chitosan and methyl cellulose), where it ranged from <10 s to several minutes. Mechanical properties investigated through texture analysis (hardness, adhesiveness, and cohesiveness) were dependent on composition. Promising spreading-ability, mucoadhesion, transcorneal permeation of L-carnosine, high ocular tolerability, and enhanced corneal epithelium wound healing were recorded for poloxamer 407/chitosan systems. CONCLUSION: In situ gelling systems comprising combinations of poloxamer-chitosan exhibited superior gelation time and temperature, mucoadhesion, and rheological characteristics suitable for effective long-acting drug delivery systems for corneal wounds

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0 ± 2.4 nm to 257.2 ± 18.6 nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10 mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p < 0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P &lt; 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples

Chitosan/Solid-Lipid Nanoparticles Hybrid Gels for Vaginal Delivery of Estradiol for Management of Vaginal Menopausal Symptoms

Hormonal replacement therapy is the mainstay treatment to improve quality of life and reduce mortality. With the increasing number of young women with early menopause, women now live longer (increased life expectancy). However, poor patient compliance with oral estrogen therapy has emerged. Intravaginal estrogen therapy can provide significant benefits with minimal risk for postmenopausal women with symptoms of the lower urinary tract and vaginal area but who do not want to take oral estrogen. In this study, estradiol-loaded solid lipid nanoparticles (SLPs) were prepared from compritol ATO 888 and precirol ATO 5, and two different stabilizers (Pluronic F127 and Tween 80) were studied. Selected SLPs (F3 and F6) were coated with different concentrations of the mucoadhesive and sustained-release polymer chitosan. Furthermore, gelation time, viscosity, mucoadhesion, ex vivo permeation, and in vitro irritation for vaginal irritation were studied. Particle sizes ranged between 450–850 nm, and EE% recorded 50–83% for the six SLPs depending on the type and amount of lipids used. Cumulative % drug release was significantly enhanced and was recorded at 51% to 83%, compared to that (less than 20%) for the control suspension of estradiol. Furthermore, extensive thermal gelation and mucoadhesion were recorded for chitosan-coated SLPs. Up to 2.2-fold increases in the permeation parameters for SLPs gels compared to the control suspension gel were recorded, revealing a slight to moderate irritation on Hela cell lines. These findings demonstrated chitosan-coated estradiol SLPs as novel and promising vaginal mucoadhesive hybrid nanogels

Design, Preparation and Evaluation of Supramolecular Complexes with Curcumin for Enhanced Cytotoxicity in Breast Cancer Cell Lines

Curcumin is one of the most researched phytochemicals by pharmacologists and formulation scientists to unleash its potential therapeutic benefits and tackle inherent biopharmaceutic problems. In this study, the native β-cyclodextrin (CD) and three derivatives, namely, Captisol (sulfobutyl ether β-CD), hydroxypropyl β-cyclodextrin, and hydroxyethyl β-cyclodextrin were investigated for inclusion complexes with curcumin using two preparation methods (physical mixing and solvent evaporation). The prepared complexes were studied for docking, solubility, FTIR, DSC, XRD, and dissolution rates. The best-fitting curcumin: cyclodextrins (the latter of the two CDs) were evaluated for cytotoxicity using human breast cell lines (MCF-7). Dose-dependent cytotoxicity was recorded as IC50% for curcumin, curcumin: hydroxyethyl β-cyclodextrin, and curcumin: hydroxypropyl β-cyclodextrin were 7.33, 7.28, and 19.05 µg/mL, respectively. These research findings indicate a protective role for the curcumin: hydroxypropyl β-cyclodextrin complex on the direct cell lines of MCF-7

Solulan C24- and Bile Salts-Modified Niosomes for New Ciprofloxacin Mannich Base for Combatting Pseudomonas-Infected Corneal Ulcer in Rabbits

Keratitis is a global health issue that claims the eye sight of millions of people every year. Dry eye, contact lens wearing and refractive surgeries are among the most common causes. The resistance rate among fluoroquinolone antibiotics is &gt;30%. This study aims at formulating a newly synthesized ciprofloxacin derivative (2b) niosomes and Solulan C24-, sodium cholate- and deoxycholate-modified niosomes. The prepared niosomal dispersions were characterized macroscopically and microscopically (SEM) and by percentage entrapment efficiency, in vitro release and drug release kinetics. While the inclusion of Solulan C24 produced something discoidal-shaped with a larger diameter, both cholate and deoxycholate were unsuccessful in forming niosomes dispersions. Conventional niosomes and discomes (Solulan C24-modified niosomes) were selected for further investigation. A corneal ulcer model inoculated with colonies of Pseudomonas aeruginosa in rabbits was developed to evaluate the effectiveness of keratitis treatment of the 2b-loaded niosomes and 2b-loaded discomes compared with Ciprocin&reg; (ciprofloxacin) eye drops and control 2b suspension. The histological documentation and assessment of gene expression of the inflammatory markers (IL-6, IL1B, TNF&alpha; and NF-&kappa;B) indicated that both 2b niosomes and discomes were superior treatments and can be formulated at physiological pH 7.4 compatible with the ocular surface, compared to both 2b suspension and Ciprocin&reg; eye drops