In vitro screening of natural product-based compounds for leishmanicidal activity.

Leishmaniasis is one of the major parasitic diseases, caused by obligate intracellular protozoa Leishmania, having high mortality as well as morbidity rate. As there is no human licensed vaccine available against leishmaniasis, chemotherapy remains the major way of combating this disease. Many disadvantages are known to be associated with the current drug regime including severe side effects and toxicity, long duration and expensive treatment, and the emergence of resistance. An alternative approach is being utilized to search for active molecules using natural sources, rather than relying on synthetic drugs. Many plant-derived secondary metabolites like phenolic compounds, steroids, quinones, etc. are being extensively investigated for their anti-leishmanial potential. One such group of complex phenolic compounds are diarylheptanoids. These compounds have been shown to exhibit anti-inflammatory, anti-parasitic, anti-fungal, and other pharmacological activities. In the present study, a set of sixteen tetrahydropyran derivatives including three natural products were obtained in lyophilized form. These compounds with trans-2,6-disubstituted tetrahydropyrans, Diospongin A, Diospongin B (isolated from Dioscorea spongiosa) and Centrolobine (Centrolobium sclerophyllum) as parent compounds were synthesized by the reaction of 1-phenyl-1-triemthylsiloxyethylene with six-membered cyclic hemiacetals in the presence of iodine as a catalyst. All the sixteen synthesized tetrahydropyran derivatives were used for toxicity analysis against L. donovani promastigotes, amastigotes and THP-1-derived human macrophages. IC50 values and selectivity index were calculated for all the compounds. Out of these sixteen, five compounds showed the best effect in vitro in terms of both leishmanicidal activity and non-toxicity to human macrophages.

Cefuroxime axetil loaded gastroretentive floating tabletsbased on hydrophilic polymers: preparation and in vitro evaluation

The aim of this work was to study the formulation and in vitro characterization of hydro dynamically balanced floating matrix tablets using Cefuroxime axetil (CA) as model drug. Different excipients such as hydroxy propyl methyl cellulose (HPMC) K15M, E5LV (gelling agent), sodium bicarbonate (gas generating agent) and sodium lauryl sulfate (SLS) (solubility enhancer) were used in order to optimize the drug release profile as well as floating property. Decrease in release characteristics with high viscous polymer were observed due to increased gel strength, tortuosity and length of drug diffusion path. Significant difference (p<0.5) in release rate was found at different concentration of SLS. The release mechanisms were explored and explained with zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The release rate, extent and mechanism were governed by the content of polymer. The polymer content and amount of floating agent significantly affected the time required for 50%of drug release (t50%), mean dissolution time (MDT), release rate constant, and diffusion exponent (n).Kinetic modeling of dissolution profile revealed that the drug release mechanism could range from diffusion controlled to case II transport, which was co-dominated by diffusion polymer erosion in the release mechanism.