Influence of the hydrophilic corona block on drug encapsulation during polymerization induced self-assembly

Block copolymer nanoparticles (PNPs) are effective for delivering hydrophobic drugs within the body due to their versatility in functionality and morphology. Recently, polymerization induced self-assembly (PISA) has emerged as an efficient and facile method for synthesizing PNPs. During PISA, polymerization, self-assembly, and drug encapsulation occur simultaneously. This simplified protocol achieves high PNP concentrations while avoiding the use of toxic organic solvents. However, the mechanism of drug encapsulation during PISA remains an open question. Previously, we found that the targeted drug concentration governed both the PNP morphology and drug encapsulation efficiency. In contrast, the hydrophobic core block molar mass affected the morphology, but had minimal influence on encapsulation efficiency. Here, we investigate how the hydrophilic corona affects drug encapsulation in PISA PNPs. The model block copolymer is poly(ethylene glycol) methyl ether-block-poly(2-hydroxypropyl methacrylate), while the model drug is phenylacetic acid. PNP morphology is characterized using transmission electron microscopy, small angle X-ray scattering, and dynamic light scattering. Drug encapsulation efficiency is quantified through ¹H nuclear magnetic resonance diffusion-ordered spectroscopy. Through systematic determinations of morphology and encapsulation efficiency, we derive a stronger understanding of the relationship between PNP structure and sequestration during PISA.