Development and optimisation of mucoadhesive nanoparticles of acyclovir using design of experiments approach.

The aim of our study was to improve the bioavailability of acyclovir (ACV) by delivery of mucoadhesive nanoparticles (NPs) and controlled delivery of drug at its absorption window. Central composite design was used by which the effects of independent variables (gelatin and Pluronic F-68) on various responses such as particle size, polydispersity index, entrapment efficiency, loading efficiency, drug release and mucoadhesive strength were studied. The optimised formulation was evaluated for morphology, stability, pharmacokinetic and gastrointestinal tracking. The optimised NPs were found to be nearly spherical. Changes in characteristics of NPs were not significant after six months of accelerated stability studies. In vivo mucoadhesion study showed significant retention of mucoadhesive NPs in upper gastro-intestinal tract for more than 12 h. Pharmacokinetic study in rats revealed that mucoadhesive NPs could maintain relatively steady plasma concentration of ACV for more than 10 h. The AUC0-∞ and mean residence time of optimised formulation (7527.9 ng h/mL and 12.09 h) were significantly high than tablet dispersion (3841.13 ng h/mL and 7.97 h).

Effective parameters for formulation of gastro adhesive nanoparticles: screening by design-of-experiments approach.

The objective of this study was selection of most influential variable for the preparation of gastro adhesive nanoparticles of acyclovir. Effect of formulation and processing variables on various response variables were studied by a Taguchi standard orthogonal array L8 design. Independent variables studied were the amount of gelatin, amount of glutaraldehyde, amount of Pluronic F-68, acetone addition rate, pH, stirring time and stirring speed. The size of all nanoparticulate formulations prepared as per the experimental design (Taguchi screening design) varied between 165 and 1610 nm, PDI between 0.360 and 1.00, Q6 between 7.31-34.93%, T60% between 19.2-37.6 h, entrapment efficiency between 15.70 and 83.12%, loading efficiency between 39.72 and 80.49% and mucoadhesive strength between 3.959-11.02 g. Pareto ranking analyses showed that the two most important factors affecting the selected responses were amount of gelatin and amount of Pluronic F-68 (p < 0.05).

Acute and sub-acute toxicity studies of Passiflora nepalensis in rats

This study was designed to elucidate the toxicity of widely used plant Passiflora nepalensis Walp. (Passifloraceae) in rats. We have taken methanolic extract isolated from whole plant of Passiflora nepalensis and studied their toxic effects. Acute, sub-acute toxicities and LD50 values were determined in experimental rats. The external appearance of the dead animals, the appearance of the viscera, heart, lungs, stomach, intestine, liver, kidney, spleen and brain were carefully noted and any apparent and significant features or differences from the normal were recorded after acute treatment with methanolic extract of whole plant of Passiflora nepalensis (MPN). Following the sub-acute administration of MPN for fourteen days, the vital organ such as liver, kidney and heart were carefully evaluated by histopathological and biochemical studies and any apparent and significant changes or differences from the normal were recorded. Pathologically, neither gross abnormalities nor histopathological changes were observed. Oral administration of MPN at the doses of 40, 80, 160 and 320 mg/kg body wt for fourteen consecutive days to male and female rats did not induce any short term toxicity. Collectively, these data demonstrate that the methanolic extract of Passiflora nepalensis have a high margin of safety.

Cardioprotective effect of Bombax ceiba flowers against acute adriamycin-induced myocardial infarction in rats

The present study was designed to evaluate the cardioprotective potential of aqueous flower extract of Bombax ceiba L., Malvaceae (BC), on the basis of biochemical and histopathological parameters in Adriamycin (Adr) induced myocardial infarction in rats and to compare with vitamin E, a known cardioprotective antioxidant. Male Wister rats were used as in vivo model for the study. BC was administered orally to Wister rats at different doses (150 mg/kg, 300 mg/kg and 450 mg/kg, b.w.) for six days/week for four weeks. Thereafter, all the groups except saline were administered Adr (20 mg/kg, i.p.). There was a significant decrease in myocardial superoxide dismutase, catalase and reduced glutathione in animals treated with Adr. Concurrently marked increase in extent of lipid peroxidation was reported. Co-treatment of BC/vitamin E and Adr resulted in an increase in the cardiac antioxidant enzymes and reduction in lipid peroxidation as compared to Adr-treated animals. Adr showed significant decrease (p<0.001) in the level of cardiac marker enzymes [Lactate dehydrogenase (LDH) and Serum glutamic oxaloacetic transaminase (SGOT)] in heart homogenate with corresponding increase in their level in serum. In BC/vitamin E treated groups significant increase (p<0.001) of LDH in heart homogenate and decrease of SGOT and LDH in serum were observed. Microscopic studies in Adr-treated animals revealed mitochondrial swelling, leukocyte infiltration, lipid inclusions and myofibrillar loss whereas the pre-treatment with BC/vitamin E led to a lesser degree of Adr-induced histological alterations. These findings suggest that aqueous flower extract of BC has protective effect against Adr-induced cardiotoxicity and may have potential as a cardioprotective agent.