Polymersomes based on a fumaric copolymer as a novel drug nanocarrier

Abstract

There is significant interest in using nanoparticles as new platforms for transporting and releasing drugs with limitations when directly administered into the body. In our research, we developed a platform for encapsulating risedronate using polymersomes obtained by self-assembly of a new triblock amphiphilic copolymer. This copolymer is based on polyethylene glycol (PEG) as a hydrophilic block and a statistical copolymer of vinyl benzoate (VBz) and diisopropyl fumarate (DIPF) as a hydrophobic block. The amphiphilic copolymer, synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT), presented a hydrophilic block fraction mass percentage (f) of 30, which is suitable for forming vesicles through self-assembly. We obtained vesicles of approximately 54 nm using the solvent injection method, with a Z-average hydrodynamic diameter of 163 nm. Compared to the vesicles obtained from a copolymer without DIPF, the nanoparticles were smaller with a narrower size distribution. To assess the potential of these systems as a vehicle for bisphosphonates, we prepared risedronate-loaded polymersomes. The resulting particles had a similar size to their uncharged counterparts, with a risedronate content of 12 ± 2 mg per gram of polymer, as determined by HPLC. Delivery studies demonstrated sustained release of risedronate for up to 10 days. We also evaluated cell viability and cytotoxicity using murine monocyte-macrophage RAW264.7 cells. The empty or risedronate-loaded nanoparticles did not affect cell proliferation, viability, and nitric oxide production at the tested concentrations. However, the particles partially inhibited nitric oxide production induced by lipopolysaccharide (LPS) in macrophages.