Doxorubicin-loaded micelles of amphiphilic diblock copolymer with pendant dendron improve antitumor efficacy: In vitro and in vivo studies

Abstract

Previously reported amphiphilic diblock copolymer with pendant dendron moieties (P₇₁D₃) has been further evaluated in tumor-bearing mice as a potential drug carrier. This P₇₁D₃-based micelle of an average diameter of 100nm was found to be biocompatible, non-toxic and physically stable in colloidal system up to 15days. It enhanced the in vitro potency of doxorubicin (DOX) in 4T1 breast tumor cells by increasing its uptake, by 3-fold, compared to free DOX. In 4T1 tumor-bearing mice, the tumor growth rate of P₇₁D₃/DOX (2mg/kg DOX equivalent) treated group was significantly delayed and their tumor volume was significantly reduced by 1.5-fold compared to those treated with free DOX. The biodistribution studies indicated that P₇₁D₃/DOX enhanced accumulation of DOX in tumor by 5- and 2-fold higher than free DOX treated mice at 15min and 1h post-administration, respectively. These results suggest that P₇₁D₃ micelle is a promising nanocarrier for chemotherapeutic agents.

Keywords: Anticancer; Biodistribution; Diblock copolymer micelles; Doxorubicin; Drug delivery.