Exploring the Potent Combination of Quercetin-Boronic Acid, Epalrestat, and Urea Containing Nanoethosomal Keratolytic Gel for the Treatment of Diabetic Neuropathic Pain: In Vitro and In Vivo Studies.

Transdermal penetration of therapeutic moieties from topical dosage forms always remains a challenge due to the presence of permeation impeding keratin which should be addressed. The purpose of the study was to formulate quercetin and 4-formyl phenyl boronic acid (QB complex) used for the preparation of nanoethosomal keratolytic gel (EF3-G). The QB complex was confirmed by Fourier transform infrared spectroscopy while skin permeation, viscosity, and epalrestat entrapment efficiency were used for the optimization of nanoethosomal gel. The keratolytic effect of the proposed nanoethosomal gel with urea (QB + EPL + U) was calculated in rat and snake skin. The spherical shape of nanoethosomes was confirmed by scanning electron microscopy. According to the findings of stability studies, viscosity decreases as temperature increases, proving their thermal stability. The negative charge of optimized EF3 with 0.7 PDI proved narrow particle size distribution with homogeneity. Optimized EF3 showed two folds increase of epalrestat permeation in highly keratinized snake skin as compared to rats' skin after 24 h. Antioxidant behaviors of EF3 (QB) > QB complex > quercetin > ascorbic acid proved reduction of oxidative stress in DPPH reduction analysis. Interestingly, the hot plate and cold allodynia test in the diabetic neuropathic rat model reduced 3-fold pain as compared to the diabetic control group which was further confirmed by in vivo biochemical studies even after the eight week. Conclusively, ureal keratolysis, primary dermal irritation index reduction, and improved loading of epalrestat render the nanoethosomal gel (EF3-G) ideal for the treatment of diabetic neuropathic pain.

Formulation, optimization and in vitro evaluation of sustained release oral hydrogels of diacerein to treat arthritis.

The current study is aimed to formulate pH responsive polymeric hydrogels. Potassium per sulphate and Methylene bis acrylamide were employed as initiator and cross linker respectively. To determine the effect of substrate on degree of cross linking different ratios of the acrylic acid (AA), potassium per sulphate (KPS) and methylenebisacrylamide (MBA) were used. Swelling experiments were conducted in both basic and acidic media. Phosphate buffer of pH 7.4 and 0.1N HCl solution were used for swelling experiment of hydrogels. The hydrogels were more responsive towards basic medium as compared to acidic environment. Formulations were also evaluated for In vitro evaluation. Diacerein was selected model drug for hydrogel. Release pattern of the diacerein was studied both in acidic (0.1N HCl solution) and basic medium. Percentage drug release from M3 formulation showed as cross linker concentration increase (0.03%) drug release decrease Hydrogel samples were characterized by FTIR to confirm the functional groups of the hydrogels and their components and scanning electron spectroscopy (SEM) was performed to characterize the structure or morphology of the hydrogels. Finally, the dissolution studies were performed to evaluate the sustain release property of the hydrogel samples. Results show that all formulations of hydrogels are pH-sensitive and follow zero-order kinetics for drug release. Hence, optimized nexus (M3) serves as excellent carrier for target drug delivery.

Formulation and assessment of controlled release tablets of famotidine by using eudragit RL 100 polymer.

Controlled release in drug release kinetics denotes reproducibility and predictability, implying that drug release from delivery devices follows a kinetically predictable and repeatable rate profile from dose to dose. In the current study controlled release tablets of famotidine were prepared by direct compression technique using Eudragit RL 100 polymer. Four different formulations of controlled release tablets of famotidine as (F1, F2, F3 and F4) were prepared by adding different drug to polymer ratio. The pre compression and the post compression of the formulation, characteristics were compared. All results obtained were within the specified standard limits. FTIR studies showed that both the drug and the polymer were compatible. In vitro dissolution study were conducted by Method II (Paddle Method) in phosphate buffer (pH 7.4), at 100rpm. Power law kinetic model was applied for drug release mechanism. The difference similarity of the dissolution profile was determined. The formulation F1 and F2 were released 97 and 96 % in 24 hours and other formulations F3 and F4 were released subsequently 93% and 90% in 24 hours. The results showed that incorporation of Eudragit RL 100 in the formulation of controlled release tablets prolong the drug release rates for 24 hours. The release mechanism was Non-Fickian diffusion mechanism. It was deducted from the current study that the Eudragit RL 100 can be efficiently incorporated in the formulation of controlled release dosage forms with predictable kinetics.

Phytochemical investigations and biological work on aerial parts and roots of Trigonella polycerata.

The purpose of this study was to purify the phytoconstituents and to explore the antibacterial, antifungal, phytotoxic and cytotoxic potential of dichloromethane and methanol extracts of aerial and root parts of Trigonella polycerata. The phytochemical study on methanol extract of aerial parts of the plant led to the isolation and purification of seven compounds that were identified as 3,4-dimethoxycinnamaldehyde, Trigocoumarin, 6,7,8-trimethoxycoumarin, Penduletin, 5-hydroxy-3,6,7,4´-tetramethoxyflavone, 3,5,7-trihydroxy-6,4-dimethoxyflavone and 5-hydroxy-4,7-dimethoxyflavone. These structures were elucidated by interpretation of EI-MS and NMR spectral data. The plant aerial parts methanol extract (TPAM) demonstrated higher antibacterial (78.99%), phytotoxic (85% growth regulation at 1000µg/mL) and cytotoxic activities (LD50: 45.643µg/mL). While the methanol root extract (TPRM) was highly active against bacteria's; Salmonella typhi (71.56%), Staphylococcus aureus (70.15%), Escherichia coli (69%), fungi like Candida albicans (70.21%) and moderately active against Brine shrimp larvae (LD50: 125.663µg/mL). The dichloromethane aerial (TPAD) and root (TPRD) extracts exhibited significant antibacterial (78.03% and 50.21% inhibitions respectively) and phytotoxic (55% growth regulation at 1000µg/mL) potential. Only TPAD indicated the best inhibition against fungi; Aspergillus flavus (75.31%) and moderate inhibition against Microsporum canis (42.21%). This phytochemical and biological work is the first time reported in Trigonella polycerata.

Meloxicam loaded hydroxypropyl methylcellulose (HPMC) microparticulate: Fabrication, characterization and in vivo pharmacokinetic assessment.

Meloxicam (MEL) is an oxicam derivative with low water solubility that is useful in the treatment of colorectal cancer (CRC) as a COX-2 inhibitor. MEL-loaded HPMC micro particles were fabricated using an oil-in-oil (o/o) emulsion solvent evaporation (ESE) method. FTIR, XRD, particle size analysis, DSC, SEM and in vitro dissolution investigation were utilized to evaluate the produced micro particles physiochemically. Finally, rabbits were used as animal models in an in vivo pharmacokinetic study to assess the MEL concentration in the plasma of rabbits. Pure MEL, F1 and F2 were given to rabbits by a single dose for in vivo pharmacokinetic investigations. The XRD and DSC results confirmed the transformation of MEL from its crystalline nature to the amorphous state in micro particles. The formulations F1 and F2 particle sizes were determined 92.43µm and 163.26µm, respectively. The prepared micro particles had a smooth, non-porous and spherical surface. In comparison to the pure drug (22.4%), the F1 and F2 cumulative drug release (%) was 86.19% and 79.57%, respectively. Pure MEL, F1 and F2 have estimated Cmax values of 7.21, 25.41 and 22.38µg/mL, respectively. MEL had a half-life of 19.98 hours, which rose to 22.19 hours and 24.75 hours for F1 and F2, respectively. MEL, F1 and F2 had AUC0-α values of 116.034, 445.95 and 462.72µg/mL*h, respectively. Considering these aspects, MEL-loaded HPMC micro particles may have the potential to better the delivery and control the release of drug that is not easily dissolved in water which could lead to improved therapeutic efficacy and limited side effects.

Evaluation of cardio protective, anti-inflammatory, analgesic and CNS depressant activity of Grewia asiatica L. fruit extract.

Grewia asiatica L. is a potential medicinal plant used for various diseases in traditional medicine. Current study was aimed to evaluate the cardio protective, anti-inflammatory, analgesic and CNS depressant activities of Grewia asiatica L. fruit extract. In cardio protective activity myocardial injury was produced by injection of Isoproterenol (200 mg/kg, s.c), G. asiatica 250 and 500mg/kg treated groups significantly (p<0.05) decreased the level of serum AST, ALT, LDH and CKMB, hence produced cardio protective effect. In analgesic activities G. asiatica produced significant (p<0.05) analgesic effects in acetic acid induced writhing, formalin, paw pressure and tail immersion test. G. asiatica at 250 and 500mg/kg oral dose, significantly (p<0.05) reduced the rat paw edema in carrageen an induced rat paw edema test. G. asiatica extract also produced significant CNS depressant effects in open field, hole board and thiopental sodium induced sleeping time. Findings of the current study suggest that G. asiatica fruit extract showed potential pharmacological effects and can be utilized in alternative medicine.

Microwave-Treated Physically Cross-Linked Sodium Alginate and Sodium Carboxymethyl Cellulose Blend Polymer Film for Open Incision Wound Healing in Diabetic Animals-A Novel Perspective for Skin Tissue Regeneration Application.

This study aimed at developing the microwave-treated, physically cross-linked polymer blend film, optimizing the microwave treatment time, and testing for physicochemical attributes and wound healing potential in diabetic animals. Microwave-treated and untreated films were prepared by the solution casting method and characterized for various attributes required by a wound healing platform. The optimized formulation was tested for skin regeneration potential in the diabetes-induced open-incision animal model. The results indicated that the optimized polymer film formulation (MB-3) has significantly enhanced physicochemical properties such as high moisture adsorption (154.6 ± 4.23%), decreased the water vapor transmission rate (WVTR) value of (53.0 ± 2.8 g/m2/h) and water vapor permeability (WVP) value (1.74 ± 0.08 g mm/h/m2), delayed erosion (18.69 ± 4.74%), high water uptake, smooth and homogenous surface morphology, higher tensile strength (56.84 ± 1.19 MPa), and increased glass transition temperature and enthalpy (through polymer hydrophilic functional groups depicting efficient cross-linking). The in vivo data on day 16 of post-wounding indicated that the wound healing occurred faster with significantly increased percent re-epithelialization and enhanced collagen deposition with optimized MB-3 film application compared with the untreated group. The study concluded that the microwave-treated polymer blend films have sufficiently enhanced physical properties, making them an effective candidate for ameliorating the diabetic wound healing process and hastening skin tissue regeneration.

Optimization of Chitosan-Decorated Solid Lipid Nanoparticles for Improved Flurbiprofen Transdermal Delivery.

Transdermal delivery is a potential alternative route to oral administration for drugs associated with stomach discomfort, such as flurbiprofen, a widely nonsteroidal anti-inflammatory drug (NSAID). This study aimed to design solid lipid nanoparticle (SLN) transdermal formulations of flurbiprofen. Chitosan-coated SLNs were prepared by the solvent emulsification method, and their properties and permeation profiles across the excised rat skin were characterized. The particle size of uncoated SLNs was at 695 ± 4.65 nm, which increased to 714 ± 6.13, 847 ± 5.38, and 900 ± 8.65 nm upon coating with 0.05, 0.10, and 0.20% of chitosan, respectively. The drug association efficiency was improved when a higher concentration of chitosan was employed over SLN droplets that endowed a higher affinity of flurbiprofen with chitosan. The drug release was significantly retarded as compared to the uncoated entities and followed non-Fickian anomalous diffusion that was depicted by "n" values of >0.5 and <1. Also, the total permeation of chitosan-coated SLNs (F7-F9) was significantly higher than that of the noncoated formulation (F5). Overall, this study has successfully designed a suitable carrier system of chitosan-coated SLNs that provide insight into the current conventional therapeutic approaches and suggest new directions for the advancements in transdermal drug delivery systems for improved permeation of flurbiprofen.

An Investigation for Skin Tissue Regeneration Enhancement/Augmentation by Curcumin-Loaded Self-Emulsifying Drug Delivery System (SEDDS).

Diabetes, one of the global metabolic disorders, is often associated with delayed wound healing due to the elevated level of free radicals at the wound site, which hampers skin regeneration. This study aimed at developing a curcumin-loaded self-emulsifying drug delivery system (SEDDS) for diabetic wound healing and skin tissue regeneration. For this purpose, various curcumin-loaded SEDDS formulations were prepared and optimized. Then, the SEDDS formulations were characterized by the emulsion droplet size, surface charge, drug content/entrapment efficiency, drug release, and stability. In vitro, the formulations were assessed for the cellular uptake, cytotoxicity, cell migration, and inhibition of the intracellular ROS production in the NIH3T3 fibroblasts. In vivo, the formulations' wound healing and skin regeneration potential were evaluated on the induced diabetic rats. The results indicated that, after being dispersed in the aqueous medium, the optimized SEDDS formulation was readily emulsified and formed a homogenous dispersion with a droplet size of 37.29 ± 3.47 nm, surface charge of -20.75 ± 0.07 mV, and PDI value of less than 0.3. The drug content in the optimized formulation was found to be 70.51% ± 2.31%, with an encapsulation efficiency of 87.36% ± 0.61%. The SEDDS showed a delayed drug release pattern compared to the pure drug solution, and the drug release rate followed the Fickian diffusion kinetically. In the cell culture, the formulations showed lower cytotoxicity, higher cellular uptake, and increased ROS production inhibition, and promoted the cell migration in the scratch assay compared to the pure drug. The in vivo data indicated that the curcumin-loaded SEDDS-treated diabetic rats had significantly faster-wound healing and re-epithelialization compared with the untreated and pure drug-treated groups. Our findings in this work suggest that the curcumin-loaded SEDDS might have great potential in facilitating diabetic wound healing and skin tissue regeneration.