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Abstract #90627 Published in IGR 21-3
Effects of shell thickness of hollow poly(lactic acid) nanoparticles on sustained drug delivery for pharmacological treatment of glaucoma
Nguyen DD; Nguyen DD; Luo LJ; Lai JYActa biomaterialia 2020; 111: 302-315
Structural designing of carriers with extended drug release profiles is critically important for achieving long-acting drug delivery systems toward efficient managements of chronic diseases. Here, we present a strategy to exploit the effects of the shell thickness of hollow poly(lactic acid) nanoparticles (HPLA NPs) in sustained glaucoma therapy. Formulations based on pilocarpine-loaded HPLA NPs with tailorable shell thickness ranging from 10 to 100 nm were shown to be highly compatible with human lens epithelial cells in vitro and with rabbit eyes in vivo. Specifically, shell thickness regulated the release of pilocarpine, with thick shells (~70 to 100 nm) providing sustained drug release performance but limited drug-loading efficiency, whereas ultrathin shells (~10 nm) induced the opposite effects. Remarkably, moderately thick shells (~40 nm) showed the most effective release profile of pilocarpine (above the therapeutic levels of ~10 µg/mL for over 56 days). In a rabbit model of glaucoma, single intracameral administration of an HPLA NP-based formulation with shell thickness of ~40 nm sustainably alleviated ocular hypertension for over 56 days, consequently protecting the structural integrity of the corneal endothelium, preserving the electrophysiological functions of the retina, and attenuating retinal and optic nerve degeneration in progressively glaucomatous eyes. The findings therefore implied a promising use of shell thickness effects in the development of long-acting drug delivery systems for pharmacological treatment of chronic ocular diseases. STATEMENT OF SIGNIFICANCE: Owing to their large surface areas and modifiable structures, nanoparticles have been considered as a promising platform for drug delivery; however, achieving drug nanocarrier systems with reduced burst release and sustained therapeutic efficacy remains challenges. This work presents the first report on rational design of hollow poly(lactic acid) nanocarriers for tailoring the structure-property-function relationships toward effective treatment of glaucoma. The shell thickness of the hollow nanocarriers is demonstrated to have influential impacts on pilocarpine encapsulation efficiency and release profile, indicating that the most sustained delivery performance (maintaining the release of pilocarpine above therapeutic level over 56 days) can be obtained for the polymeric nanoparticles with moderate shell thickness of ~40 nm.
Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
Full articleClassification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
