Polymersomes based on a fumaric copolymer as a novel drug nanocarrier

Abstract

There is significant interestin using nanoparticles as new platforms for transporting and releasing drugs withlimitations when directly administered into the body. In our research, we developed aplatform for encapsulating risedronate using polymersomes obtained byself-assembly of a new triblock amphiphilic copolymer. This copolymer is basedon polyethylene glycol (PEG) as a hydrophilic block and a statistical copolymerof vinyl benzoate (VBz) and diisopropyl fumarate (DIPF) as a hydrophobic block.The amphiphilic copolymer, synthesized by reversible addition-fragmentationchain transfer polymerization (RAFT), presented a hydrophilic block fractionmass percentage (f) of 30, which is suitable for forming vesicles throughself-assembly. We obtained vesicles of approximately54 nm using the solvent injection method, with a Z-average hydrodynamicdiameter of 163 nm. Compared to the vesicles obtained from a copolymer withoutDIPF, the nanoparticles were smaller with a narrower size distribution. Toassess the potential of these systems as a vehicle for bisphosphonates, weprepared risedronate-loaded polymersomes. The resulting particles had a similarsize to their uncharged counterparts, with a risedronate content of 12 ± 2 mgper gram of polymer, as determined by HPLC. Delivery studies demonstratedsustained release of risedronate for up to 10 days. We also evaluated cellviability and cytotoxicity using murine monocyte-macrophage RAW264.7 cells. Theempty 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 bylipopolysaccharide (LPS) in macrophages.