Self-assembled micelles prepared from poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) block copolymers for sustained release of valsartan

Poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) diblock copolymers with different compositions were synthesized by ring-opening polymerization of D,L-lactide and glycolide, using monomethoxy PEG as macro-initiator. The resulting copolymers were characterized by nuclear magnetic resonance, gel permeation chromatography, and critical micelle concentration analyses. Self-assembly of the copolymers yielded aggregates of different architectures, including spherical micelles and a mixture of spherical and worm-like micelles with Y-junctions. The self-assembled architecture depends on both the hydrophilic/hydrophobic balance and the molar mass of copolymers. Valsartan, a widely used drug in the treatment of hypertension, was loaded in micelles using a co-solvent evaporation method. High drug-loading content was obtained for worm-like micelles. in vitro drug release was performed at 37 degrees C in pH 7.4 phosphate-buffered saline. An initial burst release is detected in all cases, followed by slower release up to 9 days. The overall release rate is strongly dependent on the degradation of micelles. Copolymers with short PLGA blocks exhibit faster drug release due to faster degradation of micelles, and worm-like micelles present slower drug release as compared to spherical ones. Therefore, PLGA-PEG copolymer micelles with high drug-loading capacity, different architectures, and variable drug release rates could be most attractive for sustained delivery of valsartan.

Automated summary

PLGA-PEG diblock copolymers with varying compositions were synthesized using ring-opening polymerization, leading to the formation of micelles with different structures. These micelles were used to load valsartan for controlled drug release, with the overall release rate depending on micelle degradation.