Time-resolved SAXS studies during the synthesis of hydrolytically degradable poly(ε-caprolactone)-poly(N,N′-dimethylacrylamide) diblock copolymer nanoparticles in aqueous media

The mechanism of nanoparticle formation during reverse sequence polymerization-induced self-assembly (PISA) is studied by small-angle X-ray scattering (SAXS). More specifically, N,N′-dimethylacrylamide (DMAC) monomer is added to a trithiocarbonate-capped poly(ɛ-caprolactone) (PCL) precursor and initially polymerized in the bulk at 80 °C via reversible addition-fragmentation chain transfer (RAFT) polymerization. SAXS indicates the unexpected formation of molten PCL droplets dispersed within DMAC monomer. After 5 min (14% DMAC conversion) at 80 °C, the reaction mixture is diluted with water, and the aqueous milieu is analyzed using a flow cell. A transient lamellar phase is formed immediately after water addition that subsequently transforms into nascent spherical nanoparticles. During the remaining DMAC polymerization, the overall nanoparticle diameter remains essentially constant with a concomitant reduction in the PCL core radius and the aggregation number. This suggests that individual PCL-PDMAC chains are in equilibrium with the nanoparticles. SAXS analysis indicates that the amorphous PCL cores have a mean diameter of 8.8 nm at 80 °C: X-ray diffraction (XRD) studies confirm that such nanoscale confinement prevents their crystallization on cooling to 20 °C. Finally, this formulation can be combined with crystallization-driven self-assembly (CDSA): UV-initiated DMAC polymerization at 15 °C produces rod-like PCL-PDMAC nanoparticles with semicrystalline PCL cores.