Design of functional polymeric micelles as site-specific drug vehicles based on poly ( α-hydroxy ethylene oxide-co- β-benzyl l-aspartate) block copolymers

Abstract

Poly ( α-hydroxy ethylene oxide-co- β-benzyl l-aspartate), α-hydroxy PEO/PBLA, block copolymers were used for the formulation of new functional polymeric micelles. They have a small diameter (about 30 nm) and a very low critical micellar concentration (cmc) in water, ca. 4 mg l −1. Doxorubicin (DOX) was physically entrapped into the hydrophobic inner core of these functional micelles. The diameter of DOX-loaded α-hydroxy PEO/PBLA micelles was determined to be approximatively the same as the diameter of the corresponding empty micelles, ca. 25 nm. Moreover, the DOX-loaded functional micelles, as the corresponding empty micelles, were shown to be stable in 0.1 M phosphate buffered solution (PBS) pH 7.4 even in presence of proteins. The cytotoxicity of DOX-loaded functional micelles against P388D1 leukemia cells was studied and compared to the one of DOX-loaded α-methoxy PEO/PBLA micelles and to the cytotoxicity of both α-hydroxy and α-methoxy PEO/PBLA micelles. From this study it was concluded that the DOX-loaded functional micelles seem to have a slightly higher cytotoxicity than the DOX-loaded α-methoxy PEO/PBLA micelles, while both empty micelles were shown to be non-cytotoxic against P388D1 leukemia cells.