Boosting Drug Discovery for Parkinson's: Enhancement of the Delivery of a Monoamine Oxidase-B Inhibitor by Brain-Targeted PEGylated Polycaprolactone-Based Nanoparticles
authors Pinto, M; Fernandes, C; Martins, E; Silva, R; Benfeito, S; Cagide, F; Mendes, RE; Paz, FAA; Garrido, J; Remiao, F; Borges, F
nationality International
journal PHARMACEUTICS
author keywords Parkinson disease; chromone; monoamine oxidase B inhibitor; PEGylated nanoparticles; intestinal and brain permeability
keywords IN-VITRO TRANSPORT; POLYMERIC NANOPARTICLES; PLGA NANOPARTICLES; CONTROLLED-RELEASE; CELLULAR UPTAKE; SH-SY5Y CELLS; BARRIER; MODEL; POLY(EPSILON-CAPROLACTONE); POLYSORBATE-80
abstract The current pharmacological treatments for Parkinson's disease only offer symptomatic relief to the patients and are based on the administration of levodopa and catechol-O-methyltransferase or monoamine oxidase-B inhibitors (IMAO-B). Since the majority of drug candidates fail in pre- and clinical trials, due largely to bioavailability pitfalls, the use of polymeric nanoparticles (NPs) as drug delivery systems has been reported as an interesting tool to increase the stealth capacity of drugs or help drug candidates to surpass biological barriers, among other benefits. Thus, a novel potent, selective, and reversible IMAO-B (chromone C27, IC50 = 670 +/- 130 pM) was encapsulated in poly(caprolactone) (PCL) NPs by a nanoprecipitation process. The resulting C27-loaded PEGylated PCL NPs (similar to 213 nm) showed high stability and no cytotoxic effects in neuronal (SH-SY5Y), epithelial (Caco-2), and endothelial (hCMEC/D3) cells. An accumulation of PEGylated PCL NPs in the cytoplasm of SH-SY5Y and hCMEC/D3 cells was also observed, and their permeation across Caco-2 and hCMEC/D3 cell monolayers, used as in vitro models of the human intestine and blood-brain barrier, respectively, was demonstrated. PEGylated PCL NPs delivered C27 at concentrations higher than the MAO-B IC50 value, which provides evidence of their relevance to solving the drug discovery pitfalls.
publisher MDPI
year published 2019
volume 11
issue 7
digital object identifier (doi) 10.3390/pharmaceutics11070331
web of science category Pharmacology & Pharmacy
subject category Pharmacology & Pharmacy
unique article identifier WOS:000478995100033
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journal analysis (jcr 2017):
journal impact factor 3.746
5 year journal impact factor Not Available
category normalized journal impact factor percentile 80.268
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