Encapsulation of phenylacetic acid in polymeric nanoparticles during polymerization induced self-assembly

Amphiphilic block copolymer nanoparticles (PNPs) can behave as drug carriers for hydrophobic drugs. Polymerization induced self-assembly (PISA) is a versatile and efficient method for synthesizing PNPs. For PISA conducted in the presence of a drug, the polymerization, self-assembly, and drug encapsulation occur simultaneously. This approach simplifies synthesis and avoids the use of toxic organic solvents. The mechanism of drug encapsulation during PISA, however, remains an open question. Here, we investigate how encapsulation during PISA affects PNP structure and drug sequestration. The model block copolymer was poly(glycerol monomethacrylate)-b-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA). The model drug was phenylacetic acid, whose water solubility is 16 mg/mL. The nanostructure was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Encapsulation efficiency was quantified using a combination of DLS and ¹H nuclear magnetic resonance diffusion-ordered spectroscopy (NMR DOSY). With increasing concentration of the drug and PHPMA degree of polymerization (N_PHPMA), the PNP morphology shifted from spherical micelles to cylindrical micelles to vesicles. At a targeted drug loading of 32 mg/mL, the encapsulation efficiency reached a maximum of ~ 75%. Increasing N_PHPMA changed the nanostructure but minimally altered encapsulation efficiency, suggesting that the drug may be partitioning into the hydrophilic corona.