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

Abstract 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′ ‐dimethylacrylamide (DMAC) using a monofunctional or bifunctional trithiocarbonate‐capped poly(ϵ‐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. 1 H NMR studies confirm more than 99 % DMAC conversion while gel permeation chromatography (GPC) studies indicate well‐controlled RAFT polymerizations ( M w / M n ≤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 °C in either acidic or alkaline solution. Degradation is also observed in phosphate‐buffered saline (PBS) (pH 7.4) at 37 °C. However, no degradation is detected over a three‐month period when these nanoparticles are stored at 20 °C in deionized water (pH 6.7). Finally, PDMAC 30 ‐PCL 16 ‐PDMAC 30 nanoparticles are briefly evaluated as a dispersant for an agrochemical formulation based on a broad‐spectrum fungicide (azoxystrobin).