Novel PDLLA/PEG copolymer micelles as drug carriers

Abstract

In this study we attempted to develop a novel drug delivery system in the form of polymeric micelles. In order to obtain polymer chains with micelle forming abilities, we have proposed to produce copolymers by transesterification of poly(DL-lactic acid) (PDLLA) (as the hydrophobic segment) and polyethylene glycol (PEG) (as the hydrophilic segment). We first produced homopolymers of PDLLA with low molecular weights by condensation polymerization of DL-lactic acid. The PDLLA homopolymer with an average molecular weight of 1866 ± 100 was then transesterified with PEG with a molecular weight range of 3300-4000. By changing the ratio of PEG to PDLLA, we were able to produce copolymers with different chain structures, and therefore, with different micelle forming abilities. FTIR, 1H-NMR, DSC, and GPC studies were performed to describe the structures of these PDLLA/PEG copolymers. Micelles of these copolymers were characterized by light scattering. We selected a model drug, i.e. adriamycin, and obtained the drug loadings to the PDLLA/PEG copolymer micelles. The maximum drug loading was about 12 mg g-1. We found that these micelles were degraded in phosphate buffer (pH 7.4 and temperature 37°C) in about 5-6 weeks. We also investigated the release of adriamycin from these PDLLA/PEG micelles, and concluded that the drug release from these micelles was mainly 'degradation controlled'.