Efficient Synthesis of Hydrolytically Degradable Block Copolymer Nanoparticles via Reverse Sequence Polymerization-Induced Self-Assembly in Aqueous Media

Hydrolytically degradable block copolymer nanoparticles are prepared via reverse sequence polymerization-induced self-assembly (PISA) in aqueous media. This efficient protocol involves the reversible addition-fragmentation chain transfer (RAFT) polymerization of N,N & PRIME;-dimethylacrylamide (DMAC) using a monofunctional or bifunctional trithiocarbonate-capped poly(& epsilon;-caprolactone) (PCL) precursor. DMAC monomer is employed as a co-solvent to solubilize the hydrophobic PCL chains. At an intermediate DMAC conversion of 20-60 %, the reaction mixture is diluted with water to 10-25 % w/w solids. The growing amphiphilic block copolymer chains undergo nucleation to form sterically-stabilized PCL-core nanoparticles with PDMAC coronas. H-1 NMR studies confirm more than 99 % DMAC conversion while gel permeation chromatography (GPC) studies indicate well-controlled RAFT polymerizations (M-w/M-n & LE;1.30). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) indicate spheres of 20-120 nm diameter. As expected, hydrolytic degradation occurs within days at 37 & DEG;C in either acidic or alkaline solution. Degradation is also observed in phosphate-buffered saline (PBS) (pH 7.4) at 37 & DEG;C. However, no degradation is detected over a three-month period when these nanoparticles are stored at 20 & DEG;C in deionized water (pH 6.7). Finally, PDMAC(30)-PCL16-PDMAC(30) nanoparticles are briefly evaluated as a dispersant for an agrochemical formulation based on a broad-spectrum fungicide (azoxystrobin).