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Open AccessArticle

Boosting Drug Discovery for Parkinson’s: Enhancement of the Delivery of a Monoamine Oxidase-B Inhibitor by Brain-Targeted PEGylated Polycaprolactone-Based Nanoparticles

1
CIQUP, Departmento de Química e Bioquímica, Centro de Investigação em Química, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal
2
UCIBIO-REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal
3
Departamento de Química, CICECO-Instituto de Materiais de Aveiro, Universidade de Aveiro, 3810-193 Aveiro, Portugal
4
Departamento de Engenharia Química, Instituto Superior de Engenharia do Porto (ISEP), Instituto Politécnico do Porto, 4200-072 Porto, Portugal
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(7), 331; https://doi.org/10.3390/pharmaceutics11070331
Received: 15 May 2019 / Revised: 30 June 2019 / Accepted: 9 July 2019 / Published: 12 July 2019
(This article belongs to the Special Issue Drug Delivery across Biological Barriers)
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 (~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. View Full-Text
Keywords: Parkinson disease; chromone; monoamine oxidase B inhibitor; PEGylated nanoparticles; intestinal and brain permeability Parkinson disease; chromone; monoamine oxidase B inhibitor; PEGylated nanoparticles; intestinal and brain permeability
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Pinto, M.; Fernandes, C.; Martins, E.; Silva, R.; Benfeito, S.; Cagide, F.; Mendes, R.F.; Almeida Paz, F.A.; Garrido, J.; Remião, F.; Borges, F. Boosting Drug Discovery for Parkinson’s: Enhancement of the Delivery of a Monoamine Oxidase-B Inhibitor by Brain-Targeted PEGylated Polycaprolactone-Based Nanoparticles. Pharmaceutics 2019, 11, 331.

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