Synthesis and characterization of 3ß-substituted amides of 17a-aza-D-homo- 4-androsten-17-one as potent 5α-reductase inhibitors and antimicrobial agents.

We herein report the synthesis of 3ß-substituted amides of 17a-aza-D-homo-4-androsten-17-one (11a-11r) from commercially available Diosgenin as the starting material. The structures of newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and mass spectrometry. All the synthesized analogues were tested for their 5α- reductase inhibitory and antimicrobial activity, some of them exhibit moderate to potent activity comparable to the reference drugs. Among the synthesized derivatives the analogue (11r) 3ß-(indonlylbutanamido)-17a-aza-D-homo-4- androsten-17-one was found to be active against both 5α-reductase enzyme and microbial strains, whereas the analogue (11i) 3ß-(3,4-dimethoxy-benzamido)-17a-aza-D-homo-4-androsten-17-one was found to be the least active. The detailed 5α-reductase inhibitors and antimicrobial activities of the synthesized compounds were reported.

Nanolipid carrier-based thermoreversible gel for localized delivery of docetaxel to breast cancer.

Intratumoral and intralesional administration of anticancer drugs in gels and implantable formulations is gaining much importance on account of its advantage of site-specific delivery with highly dependable freedom from unwanted side effects. Nanolipid carriers (NLC) are the preferred vehicle due to their improved properties particularly drug loading. In the present investigation, glyceryl monostearate-oleic acid NLCs loaded with docetaxel were prepared by emulsification and ultrasonication technique and were incorporated in thermoreversible pluronic F127 gel (TRPgel) for intralesion injection to breast tissue. The NLCs were spherical particles of 113 nm size with a negative zeta potential of -32.8 and 85 % drug entrapment. In vitro drug release profile of the NLC showed 96 % drug release in 48 h following Higuchi release kinetics. NLC incorporated TRPgel showed mucoadhesive force of 3.07 dynes/cm2 and gelling temperature in the range of 32 to 37 °C. The drug entrapped gel was also subjected to in vitro cytotoxicity study in human B-16 and HeLa cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo drug distribution study in breast tissue in healthy Wistar rats. The MTT assay revealed that docetaxel-loaded NLC incorporated into gel showed lower cytotoxicity than docetaxel. However, in vivo breast tissue distribution studies showed high tissue drug concentration, sustained over a period of 60 h in comparison to docetaxel and docetaxel-loaded NLCs. These results suggest that nanolipid carrier of docetaxel in TRPgel could be a promising carrier system to deliver drug to tumor by intralesional administration for improving therapeutic benefits of docetaxel.

Optimization of protocell of silica nanoparticles using 3² factorial designs.

The purpose of the research is to carry out systemic optimization of protocells (liposomes entrapped with silica particles). Optimization was carried out using 3(2) factorial designs for the selection of the optimized protocell composition with reference to particle size distribution and zetapotential. This design was carried out to study the effect of independent variables such as molar ratio of phosphatidylcholine to cholesterol and concentration of silica nanoparticles. A total of nine formulations of protocells were prepared and analyzed using Design expert® software from Stat-Ease, Inc. (Version 8.0.4.1 trial 2010) for the selection of the optimized combination. Contour plots were constructed with independent variables like size and potential. Protocell with 7:3 ratio of phosphatidyl choline to cholesterol and 0.5 mg/ml of silica nanoparticles demonstrated better colloidal behaviors. The findings obtained from the software corresponding to independent variables demonstrated accurate means for the optimization of the pharmaceutical formulations.