Novel polymeric micelles based on the amphiphilic diblock copolymer poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide).

摘要

PURPOSE: The purpose of this work was to synthesize a new amphiphilic diblock copolymer of poly(N-vinyl-2-pyrrolidone and poly(D,L-lactide) (PVP-b-PDLLA) capable of self-assembling into polymeric micelles with multiple binding sites and high entrapment efficiency. METHODS: The copolymer was synthesized by ring-opening polymerization of D,L-lactide initiated by potassium PVP hydroxylate. It was characterized by gel permeation chromatography, 1H- and 13C-NMR spectroscopy. The ability of the copolymer to self-assemble was demonstrated by dynamic and static light scattering, spectrofluorimetry and 1H-NMR. The hydrophobic model drug indomethacin was incorporated into the polymeric micelles by a dialysis procedure. Results. A series of amphiphilic diblock copolymers based on PVP-b-PDLLA were successfully synthesized. The critical association concentrations in water were low, always below 15 mg/L. Micellar size was generally bimodal with a predominant population between 40 and 100 nm. PVP-b-PDLLA micelles were successfully loaded with the poorly water-soluble drug indomethacin and demonstrated an entrapment efficiency higher than that observed with control poly(ethylene glycol)-b-PDLLA micelles. It was hypothesized that specific interactions with the hydrophilic outer shell could contribute to the increase in drug loading. CONCLUSION: PVP-b-PDLLA micelles appear to exhibit multiple binding sites and thus represent a promising strategy for the delivery of a variety of drugs.