Development of Novel Polymer-Lipid Hybrid Nanoparticles of Tamoxifen: In Vitro and In Vivo Evaluation
This study was undertaken to develop and investigate the effect of tamoxifen polymer-lipid hybrid nanoparticles (Tmx-PLN) on its oral bioavailability and efficacy in the 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model. Modified solvent emulsification-evaporationmethod was optimized to obtain Tmx-PLN, composed of chitosan and lecithin, of 169.66±4.84 nm particle size. The PLN exhibited prolonged In Vitro release in phosphate-buffered saline. Further, PLN displayed enhanced oral bioavailability with considerable increase in AUC (1277.46 vs. 585.01 ng/ml ·h), prolonged t 1/2 (27.87±15.62 vs. 10.18±6.5 h) and mean residence time (40.11±25.72 vs. 17.42±12.04 h) in comparison to pure Tmx. In addition, PLN exhibited significantly increased (P < 0.05) antitumor efficacy in DMBA-induced breast cancer model, when administered once in three days in comparison to Tmx daily dosing. This enhancement may be attributed to a probable reduction in Pgp efflux, decreased first-pass metabolism and lymphatic drug transport. Thus, Tmx-PLN exhibited enhanced potential to increase Tmx therapeutic efficacy in chronic treatment of breast cancer.
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Document Type: Research Article
Publication date: January 1, 2016
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