Poly(aspartic-acid) derivatives as polymeric micelle drug delivery systems

A novel amphiphilic biodegradable graft copolymer based on poly(aspartic acid) (PASP) was prepared by coupling monomethoxy poly(ethylene glycol) as the hydrophilic segment with PASP‐g‐octadecyl (PASP‐g‐OD) as the hydrophobic backbone. The critical micelle concentration of the copolymer was obtained by measuring the conductivity and fluorescence spectroscopy. Polymeric micelles were prepared with the solvent evaporation method, and the size distribution and morphology of the polymeric micelles were characterized by dynamic light scattering and transmission electron microscopy. The ability of the PASP derivatives to solubilize hydrophobic drugs was investigated using methotrexate (MTX), oleanolic acid, and podophyllotoxin (PODO) as models. The results demonstrated that drug solubility depends on the copolymer concentration, copolymer composition, as well as the physicochemical property of the drug. A stability study performed with PODO loaded by polymeric micelle solution demonstrated that the micelle carrier could protect the drug from being destroyed in a pH 7.4 buffer solution; however, the micelle did not protect it in a pH 9.5 buffer solution. Pharmacokinetic studies were carried out by intravenous administration of MTX loaded by polymeric micelle solution and MTX solution. The results demonstrated that the polymeric micelle prolonged the drug permanence in blood circulation with a mean residence time of about 2.37 times and increased the systemic bioavailability with the area under the drug concentration–time curve by about 2.34 times. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2871–2878, 2006