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Unravelling the Immunotoxicity of Polycaprolactone Nanoparticles-Effects of Polymer Molecular Weight, Hydrolysis, and Blends

2020-11Journal article Restricted access
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dc.contributor.authorJesus, Sandra
dc.contributor.authorBernardi, Natalia
dc.contributor.authorda Silva, Jessica
dc.contributor.authorColaco, Mariana
dc.contributor.authorCosta, Joao Panao
dc.contributor.authorFonte, Pedro
dc.contributor.authorBorges, Olga
dc.date.accessioned2021-06-18T16:25:46Z
dc.date.available2021-06-18T16:25:46Z
dc.date.issued2020-11
dc.description.abstractPoly-epsilon-caprolactone (PCL) is a biodegradable polyester that has FDA and CE approval as a medical device. Nonetheless, the lack of toxicity exhibited by the polymer cannot be extrapolated to its nanomaterial conformation. Despite PCL-based NPs being widely studied in the biomedical field for their advantages as controlled drug delivery systems, little data describe PCL NPs' toxicity, particularly immunotoxicity. This work assessed different PCL-based delivery systems intended for protein delivery regarding their immunotoxicity and hemocompatibility. Two different molecular weight PCL polymers were used, as well as blends with chitosan and glucan. Results showed that the presence of NaOH during the production of PCL2 NPs and PCL2/glucan NPs induced PCL alkali hydrolysis, generating more reactive groups (carboxyl and hydroxyl) that contributed to an increased toxicity of the NPs (higher reduction in peripheral blood mononuclear cell viability and lower hemocompatibility). PCL2/glucan NPs showed an anti-inflammatory activity characterized by the inhibition of LPS stimulated nitric oxide (NO) and TNF-alpha. In conclusion, generalizations among different PCL NP delivery systems must be avoided, and immunotoxicity assessments should be performed in the early stage of product development to increase the clinical success of the nanomedicine.
dc.description.sponsorshipEuropean Regional Development Fund (ERDF) through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization
dc.description.sponsorshipPortuguese national funds via FCT-Fundacao para a Ciencia e Tecnologia [POCI-01-0145-FEDER-030331, POCI-01-0145-FEDER-032610-PTDC/MEC-DER/32610/2017, UIDB/04565/2020]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1021/acs.chemrestox.0c00208
dc.identifier.issn0893-228X
dc.identifier.urihttp://hdl.handle.net/10400.1/15669
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Chemical Society
dc.subject.otherPharmacology & Pharmacy
dc.subject.otherChemistry
dc.subject.otherToxicology
dc.titleUnravelling the Immunotoxicity of Polycaprolactone Nanoparticles-Effects of Polymer Molecular Weight, Hydrolysis, and Blends
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/148805/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/157576/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/157544/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/157583/PT
oaire.citation.endPage2833
oaire.citation.issue11
oaire.citation.startPage2819
oaire.citation.titleChemical Research In Toxicology
oaire.citation.volume33
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
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project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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