title: Development of Novel Polymer-Lipid Hybrid Nanoparticles of Tamoxifen: In Vitro and In Vivo Evaluation.
abstract: 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-evaporation method 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), pro- longed t½ (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.
authors.forename: Mansingh
authors.initials: M
authors.lastname: Varthya
authors.forename: Harish
authors.initials: H
authors.lastname: Pawar
authors.forename: Charan
authors.initials: C
authors.lastname: Singh
authors.forename: Chander Parkash
authors.initials: CP
authors.lastname: Dora
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Jena
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene