PEGylated PLGA Nanoparticles As a Smart Carrier to Increase the Cellular Uptake of a Coumarin-Based Monoamine Oxidase B Inhibitor

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Fernandes, C (Author) Other; Martins, C (Author) Other; Fonseca, A (Author) Other; Nunes, R (Author) Other; Matos, MJ (Author) Other; Silva, R (Author) Other; Garrido, J (Author) Other; Sarmento, B (Author) Other; Fernando Remiao (Author) FFUP; Otero Espinar, FJ (Author) Other; Uriarte, E (Author) Other; Fernanda Borges (Author) FCUP

Journal

Title: ACS Applied Materials & Interfaces

Vol. 10

ISSN: 1944-8244

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 38 Citations

Scopus - 40 Citations

Other information

Authenticus ID: P-00P-WD2

DOI: 10.1021/acsami.8b17224

Abstract (EN): Despite research efforts to discover new drugs for Parkinson treatment, the majority of candidates fail in preclinical and clinical trials due to inadequate pharmacokinetic properties, namely blood-brain barrier permeability. Within the high demand to introduce new drugs to market, nano technology can be used as a solution. Accordingly, PEGylated PLGA nano particles (NPs) were used as a smart delivery carrier to solve the suboptimal aqueous solubility, which precludes its use in in vivo assays, of a potent, reversible, and selective monoamine oxidase B inhibitor (IMAO-B) (coumarin C75, IC50 = 28.89 +/- 1.18 nM). Long-term stable PLGA@C75 NPs were obtained by nanoprecipitation method, with sizes around 105 nm and a zeta potential of -10.1 mV. The encapsulation efficacy was around 50%, achieving the final C75 concentration of 807 +/- 30 mu M in the nano formulation, which corresponds to a therapeutic concentration 27828-fold higher than its IC50 value. Coumarin C75 showed cytotoxic effects at 50 mu M after 48 and 72 h of exposure in SH-SY5Y, Caco-2, and hCMEC/D3 cell lines. Remarkably, no cytotoxic effects were observed after nanoencapsulation. Furthermore, the data obtained from the P-gp-Glo assay and the cellular uptake studies showed that C75 is a P-glycoprotein (P-gp) substrate having a lower uptake profile in intestinal and brain endothelial cells. Moreover, it was shown that this membrane transporter influences C75 permeability profile in Caco-2 and hCMEC/D3 cells. Interestingly, PLGA NPs inhibited P-gp and were able to cross intestinal and brain membranes allowing the successful transport of C75 through this type of biological barriers. Overall, this work showed that nanotechnology can be used to solve drug discovery related drawbacks.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13