Degradability of Poly(Lactic
Acid)-Containing Nanoparticles:
Enzymatic Access through a Cross-Linked Shell Barrier
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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 cross-linking the core domain
remained accessible. Kinetic analyses by <sup>1</sup>H 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(<i>N</i>-(acryloyloxy)succinimide-<i>copolymer</i>-<i>N</i>-acryloylmorpholine)-<i>block</i>-poly(L-lactic
acid) (P(NAS-<i>co</i>-NAM)-<i>b</i>-PLLA), with
only a slight reduction to ca. 50% for the shell cross-linked 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 the development of these degradable
nanoconstructs to reach their potential for controlled release of
therapeutics and biological clearance