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

Purpose. The purpose of this work was to synthesize a new amphiphilic diblo ck copolymer of poly(N-vinyl-2-pyrrolidone and poly(D,L-lactide) (PVP-b-PDL LA) capable of self-assembling into polymeric micelles with multiple bindin g 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 g el permeation chromatography,H-1- and C-13-NMR spectroscopy. The ability of the copolymer to self-assemble was demonstrated by dynamic and static ligh t scattering, spectrofluorimetry and H-1-NMR. The hydrophobic model drug in domethacin was incorporated into the polymeric micelles by a dialysis proce dure. Results. A series of amphiphilic diblock copolymers based on PVP-b-PDLLA we re successfully synthesized. The critical association concentrations in wat er 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 dem onstrated an entrapment efficiency higher than that observed with control p oly(ethylene glycol)-b-PDLLA micelles. It was hypothesized that specific in teractions with the hydrophilic outer shell could contribute to the increas e in drug loading. Conclusion. PVP-b-PDLLA micelles appear to exhibit multiple binding sites a nd thus represent a promising strategy for the delivery of a variety of dru gs.