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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/cm 2 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.

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