Effective macrophage delivery using RAFT copolymer derived nanoparticles

Abstract

Reversible addition fragmentation chain transfer (RAFT) polymerisation provides a highly controlled means to assemble copolymers of different architectures for a variety of applications, including drug delivery. Polymers consisting of a butyl methacrylate-co-methacrylic acid p(BMA-co-MAA) hydrophobic block and a poly(ethylene glycol) methyl ether methacrylate p(PEGMA-475) hydrophilic block were synthesised via RAFT polymerisation and self-assembled into micelles. A range of micelle particles of different sizes were obtained by varying the composition of the block copolymers. The micelles were crosslinked to form nanoparticles and fluorescently labelled to study cellular internalisation. The prepared nanoparticles were extensively taken up by primary murine macrophages and a promising candidate was identified. To demonstrate effective delivery of a cell impenetrable cargo a fluorescent dye, 4′,6-diamidino-2-phenylindole (DAPI), was encapsulated inside the nanoparticles and successfully delivered to macrophages. The nanoparticles’ stability at increased temperatures and at low concentrations, the tunability of their synthesis and their extensive internalisation by macrophages and performance makes them highly promising delivery vehicles for a range of therapeutics and imaging agents.