Encapsulation of phenylacetic acid in block copolymer nanoparticles during polymerization induced self‐assembly

Abstract

Polymerization induced self-assembly (PISA) is an in situ method for producing block copolymer nanoparticles. Performing PISA in the presence of a pharmaceutical drug causes the nanoparticles to encapsulate the drug. While this approach is straightforward, the effects of drug loading and block copolymer composition remain unclear. Here, we investigate encapsulation of the drug phenylacetic acid (PA) in poly(glycerol monomethacrylate)-block-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) nanoparticles during PISA. Nanoparticle morphology is characterized by electron microscopy and light scattering, while encapsulation efficiency (p) is quantified using nuclear magnetic resonance diffusometry. Increasing the PA loading shifts the nanoparticle morphology from spherical micelles ! cylindrical micelles ! vesicles.At a 32 mg/ml PA loading, p maximizes at $80%. Increasing the PHPMA degree of polymerization minimally impacts p. The invariance of p toward core block length suggests that PA binds to the nanoparticle corona, highlighting the importance of the hydrophilic block for drug encapsulation during PISA.

Polymerization‐induced self‐assembly for drug delivery: A critical appraisal

“…106 Conducting PISA in the presence of curcumin (Figure 5, Structure II) as a model drug revealed that its presence alters the morphological evolution during the PISA process (Figure 6). Li et al 107 found similarly facilitated morphological transitions upon increasing the targeted loading with the drug PA.…”

“…Considering the challenge of solubilizing hydrophobic cargo in the reaction mixture, PISA systems that aim for physical in situ cargo encapsulation generally yield low cargo loadings. In the exceptional cases where high cargo loadings are achieved 106 and/or amphiphilic drugs such as phenylacetic acid (PA; Figure 5, Structure IV ) 107 are used, the cargo location within the nanoparticle should be considered as it may influence the NP behavior in a biological environment. The location of the cargo may not be limited to the hydrophobic core, but sequestration into the hydrophilic shell can occur 129 .…”

“…Early examples of PISA studies 127,128 neglected the impact of cargo on the polymerization kinetics and the morphological outcome. However, recent studies refuted cargo inertness 106,108 and revealed significant impact on the PISA process as a function of the physical–chemical properties of the cargo 106,107 and its concentration in the reaction mixture 97,98 . In a pioneering example, Cao et al systematically studied the influence of drug loading on the morphology of PISA‐NPs 106 .…”

“…impact on the PISA process as a function of the physicalchemical properties of the cargo 106,107 and its concentration in the reaction mixture. 97,98 In a pioneering example, Cao et al systematically studied the influence of drug loading on the morphology of PISA-NPs.…”