Degradability of Poly(Lactic Acid)-Containing Nanoparticles: Enzymatic Access through a Cross-Linked Shell Barrier

Abstract

Comparative studies of bulk samples of hydrolytically-degradable poly(lactic acid) (PLA) vs. core-shell block copolymer micelles having PLA cores revealed remarkable acceleration in the proteinase K enzymatic hydrolysis of the nanoparticulate forms, and demonstrated that even with amidation-based shell crosslinking, the core domain remained accessible. Kinetic analyses by 1H NMR spectroscopy showed less than 20% lactic acid released from enzymatically- catalyzed hydrolysis of poly(L-lactic acid) in bulk, whereas ca. 70 % of the core degraded within 48 h for block copolymer micelles of poly(N-(acryloyloxy)succinimide-copolymer-N-acryloylmorpholine)-block-poly(L-lactic acid) (P(NAS-co-NAM)-b-PLLA), with only a slight reduction to ca. 50 % for the shell crosslinked derivatives. Rigorous characterization measurements by NMR spectroscopy, fluorescence spectroscopy, dynamic light scattering, atomic force microscopy, and transmission electron microscopy were employed to confirm core excavation. These studies provide important fundamental understanding of the effects of nanoscopic dimensions on protein-polymer interactions and polymer degradability, which will guide development of these degradable nanoconstructs to reach their potential for controlled release of therapeutics and biological clearance.

Esterase-activatable β-lapachone prodrug micelles for NQO1-targeted lung cancer therapy

“…Our data show that dC 3 and dC 6 prodrugs were readily converted to β-lap inside the micelles by PLE [42], however, the dC 6 micelles had slower release kinetics of β-lap from micelles than dC 3 micelles (Fig. 3a).…”

Multi-scale analysis of the impact of polylactide morphology on gas barrier properties

“…However, proteinase K can still access to the intra-spherulite amorphous phase and hydrolyse the spherulitic superstructure. It has been shown that it can even degrade a core of polylactide trapped in a crosslinked shell [42]. The SEM pictures of the sample surfaces after enzymatic degradation are shown in Fig.…”

Prodrug Strategy to Achieve Lyophilizable, High Drug Loading Micelle Formulations Through Diester Derivatives of β‐Lapachone

“…[15] This core-based enzyme prodrug conversion also agrees with studies by Wooley et al, who reported the hydrolysis of micelle cores by proteinase K in crosslinked micelles. [16] …”