A new hydrotropic block copolymer micelle system for aqueous solubilization of paclitaxel

Paclitaxel (PTX), a potent anti-cancer drug, is poorly soluble in water, and this has been a major limitation in developing patient friendly formulations for clinical applications. Recent studies on polymeric micelles, especially hydrotropic polymer micelles, have suggested an alternative formulation of PTX based on their high loading capacity and physical stability in aqueous media. The present study aims at aqueous solubilization of PTX in polymer micelles without using any organic solvents that is usually required for solubilization in polymer micelles. Poly(ethylene glycol) was used as a hydrophilic block and, as a hydrotropic block, poly(4-(2-vinylbenzyloxy-N-picolylnicotinamide)) (P(2-VBOPNA)) was synthesized by atom transfer radical polymerization. The hydrotropic block copolymers did not form a micellar structure at pH 2 or below due to protonation of PNA groups, but the aqueous solubility of PTX increased significantly by the hydrotropic activity of P(2-VBOPNA). At pH values higher than 2, the PTX solubility increased even further due to deprotonation of 2-VBOPNA, leading to effective polymer micellization. A longer hydrotropic block resulted in higher aqueous PTX solubility, and slightly slower release rate from the micelles. The hydrotropic block copolymers synthesized in this study are able to form PTX-loaded polymeric micelles in aqueous solution without using any organic solvents. (c) 2007 Elsevier B.V. All rights reserved.