The preparation, characterization, release, and in vitro cytotoxicity of a biodegradable polymeric micellar formulation of paclictaxel (PTX) were investigated. The micelles based on thermosensitive and degradable amphiphilic polyaspartamide derivatives containing pendant aromatic structures (phe-g-PHPA-g-mPEG) were prepared by a quick heating method without using toxic organic solvent. Dynamic light-scattering results show that the micelles are stable upon dilution under physiological conditions and the destabilization of the micelles is pH-dependent and the phe-g-PHPA-g-mPEG polymers are biodegradable. PTX was loaded into the phe-gPHPAs-g-mPEG micelles with encapsulation efficiency of >90%, resulting in a high drug loading content (up to 29%). PTX-loaded micelles had a mean size around 70 nm with narrow size distribution (polydispersity index, <0.1). The PTX-loaded micelles showed sustained drug release and obvious anticancer activity similar to Taxol against HepG2 cells, whereas blank micelles were nontoxic. The present results suggest that the thermosensitive and biodegradable phe-g-PHPAg-mPEG micelles are a promising delivery system for the hydrophobic drugs. (C) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3917-3924