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

dc.contributor.authorFernandes C.
dc.contributor.authorMartins C.
dc.contributor.authorFonseca A.
dc.contributor.authorNunes R.
dc.contributor.authorMatos M.J.
dc.contributor.authorSilva R.
dc.contributor.authorGarrido J.
dc.contributor.authorSarmento B.
dc.contributor.authorRemião F.
dc.contributor.authorOtero-Espinar F.J.
dc.contributor.authorUriarte E.
dc.contributor.authorBorges F.
dc.date.accessioned2020-09-02T22:17:26Z
dc.date.available2020-09-02T22:17:26Z
dc.date.issued2018
dc.identifier10.1021/acsami.8b17224
dc.identifier.citation10, 46, 39557-39569
dc.identifier.issn19448244
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4435
dc.descriptionDespite 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, nanotechnology can be used as a solution. Accordingly, PEGylated PLGA nanoparticles (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, IC 50 = 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 μM in the nanoformulation, which corresponds to a therapeutic concentration 27828-fold higher than its IC 50 value. Coumarin C75 showed cytotoxic effects at 50 μM 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. Copyright © 2018 American Chemical Society.
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.subjectcytotoxicity
dc.subjectdrug release
dc.subjectefflux transporters
dc.subjectintestinal and brain permeability
dc.subjectMAO-B inhibitors
dc.subjectP-glycoprotein
dc.subjectParkinson's disease
dc.subjectpolymeric nanosystems
dc.subjectAssays
dc.subjectCell culture
dc.subjectClinical research
dc.subjectControlled drug delivery
dc.subjectCytotoxicity
dc.subjectDrug products
dc.subjectEndothelial cells
dc.subjectGlycoproteins
dc.subjectNanoparticles
dc.subjectBlood-brain barrier
dc.subjectDrug release
dc.subjectEfflux transporter
dc.subjectMonoamine oxidase B
dc.subjectNanoprecipitation method
dc.subjectP-glycoprotein
dc.subjectParkinson's disease
dc.subjectPharmacokinetic properties
dc.subjectTargeted drug delivery
dc.subjectamine oxidase (flavin containing)
dc.subjectcoumarin
dc.subjectcoumarin derivative
dc.subjectdrug carrier
dc.subjectmonoamine oxidase inhibitor
dc.subjectnanoparticle
dc.subjectsurfactant
dc.subjectCaco-2 cell line
dc.subjectchemistry
dc.subjecthuman
dc.subjectIC50
dc.subjectParkinson disease
dc.subjectpermeability
dc.subjectscanning electron microscopy
dc.subjecttumor cell line
dc.subjectCaco-2 Cells
dc.subjectCell Line, Tumor
dc.subjectCoumarins
dc.subjectDrug Carriers
dc.subjectHumans
dc.subjectInhibitory Concentration 50
dc.subjectMicroscopy, Electron, Scanning
dc.subjectMonoamine Oxidase
dc.subjectMonoamine Oxidase Inhibitors
dc.subjectNanoparticles
dc.subjectParkinson Disease
dc.subjectPermeability
dc.subjectPolylactic Acid-Polyglycolic Acid Copolymer
dc.subjectSurface-Active Agents
dc.titlePEGylated PLGA Nanoparticles As a Smart Carrier to Increase the Cellular Uptake of a Coumarin-Based Monoamine Oxidase B Inhibitor
dc.typeArticle


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