Preparation, characterization of paclitaxel-loaded Pluronic P105 polymeric micelles and in vitro reversal of multidrug resistant tumor.
- Author:
Yong-Zhong WANG
1
;
Xiao-Ling FANG
;
Ya-Juan LI
;
Zhi-Wen ZHANG
;
Li-Mei HAN
;
Xian-Yi SHA
Author Information
1. School of Pharmacy, Fudan University, Shanghai 200032, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents, Phytogenic;
administration & dosage;
chemistry;
pharmacology;
Cell Line, Tumor;
Drug Carriers;
Drug Delivery Systems;
Drug Resistance, Multiple;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Excipients;
chemistry;
Female;
Humans;
Inhibitory Concentration 50;
Micelles;
Ovarian Neoplasms;
metabolism;
pathology;
Paclitaxel;
administration & dosage;
chemistry;
metabolism;
pharmacology;
Particle Size;
Poloxamer;
chemistry
- From:
Acta Pharmaceutica Sinica
2008;43(6):640-646
- CountryChina
- Language:Chinese
-
Abstract:
Drug delivery system (DDS) is a novel approach to overcome multidrug resistance (MDR) in tumors nowadays. This work was designed to investigate a new micellar delivery system for in vitro reversal of resistant ovarian tumor cells, based on a nonionic triblock copolymer Pluronic P105 and paclitaxel (PTX). The PTX-loaded polymeric micelles (P105/PTX) were prepared by thin film-hydration methods. Based on the results of single factor experiments, the P105/PTX micelle formulation was optimized by employing the central composite design-response surface methodology. The physico-chemical properties of the P105/PTX micelles were characterized, including micelle size, drug loading coefficient, in vitro release behavior, etc. The cytotoxicity of the P105/PTX micelles was assessed against human ovarian tumor cell line, SKOV-3/PTX, by a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. In order to understand the possible mechanism of Pluronic effects in resistant tumor cells, cellular uptake study of micellar PTX or Rhodamine-123 (R-123) was also carried out. The results showed that the micelle size was about 24 nm with drug loading coefficient of 1.1% and PTX concentration of 700 microg x mL(-1). The cumulative release amount of PTX from the P105/PTX micelles was only 45.4% in 6 h (P < 0.05) and 79.6% in 24 h, whereas Taxol injection in 6 h released 95.2% PTX. The IC50 values of the P105/PTX micelles and Taxol injection against SKOV-3/PTX were 1.14 and 5.11 microg x mL(-1), and resistance reversion index (RRI) was 9.65 and 2.15, respectively. The micellar PTX or R-123 exhibited a significant increase in cellular uptake in resistant SKOV-3/PTX cells compared with free PTX or R-123. These results indicated that PTX could effectively be solubilized by Pluronic P105 block copolymers via thin film-hydration process and formulation optimization, producing nano-scale polymeric micelles with sustained release property in vitro. The P105/PTX micelles were effectively able to reverse resistance to PTX in SKOV-3/PTX tumor cells compared with Taxol injection or free PTX solution, and the enhanced cytotoxicity in the resistant SKOV-3/PTX cell was related to the improved cellular uptake of PTX by Pluronic P105 copolymers.
