[Preparation, characterization of paclitaxel-loaded Pluronic P105 polymeric micelles and in vitro reversal of multidrug resistant tumor].

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.

• Authors: Yong-Zhong Wang, Xiao-Ling Fang, Ya-Juan Li, Zhi-Wen Zhang, Li-Mei Han, Xian-Yi Sha
• Journal: Yao xue xue bao = Acta pharmaceutica Sinica (Yao Xue Xue Bao) Vol. 43 Issue 6 Pg. 640-6 (Jun 2008) ISSN: 0513-4870 [Print] China
• PMID: 18822969 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Drug Carriers
• Excipients
• Micelles
• Poloxamer
• pluronic P105
• Paclitaxel

Topics

• 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)