Polymersomes based on a fumaric copolymero as a novel drug nanocarrier

Abstract

There is great interest in the development of nanoparticles as new platforms for the transport and release of drugs that present drawbacks for their direct administration into the body. In this work we developeda platform for bisphosphonates encapsulation based on polymersomes. Polymersomes were obtained by self-assembly of a new triblock amphiphilic copolymer based on polyethylene glycol (PEG) as hydrophilic block, and a statistical copolymer of vinyl benzoate (VB) and diisopropyl fumarate (DIPF) ashydrophobic block. The copolymer wassynthesized by reversible addition fragmentation chain transfer polymerization (RAFT). The obtained amphiphilic polymer presented ahydrophilic block fraction mass percentage (f) of 30,appropriate for the formation of vesicles by self-assembly. Using the solvent injection method, we obtained vesicles of around 54 nm with a Z-average hydrodynamic diameter of 163 nm. The nanoparticles were smaller and with narrow size distribution than particlesformed by the counterpart copolymer without DIPF. In order to evaluate the potential of these copolymers as a vehicle for bisphosphonates, risedronate loaded polymersomes were prepared. The obtained particles showed a similar size to their uncharged analogues, with a content of 12 ± 2 mg of risedronate per g of polymer, determined by HPLC. Risedronate was delivered from the polymersomes in a sustained but controlled fashion up to 10 days. Cell viability and cytotoxicity were evaluated 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 LPS on macrophages.