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Safety evaluation of novel polymeric nanocarriers for drug delivery using human osteoblasts

dc.contributor.authorDias, Kamila
dc.contributor.authorLouro, Henriqueta
dc.contributor.authorGonçalves, Lídia
dc.contributor.authorBettencourt, Ana
dc.contributor.authorSilva, Maria João
dc.date.accessioned2017-08-02T11:07:28Z
dc.date.available2017-08-02T11:07:28Z
dc.date.issued2017-05-08
dc.description.abstractThe development of novel nanocarriers has been recognized as a promising approach to improve drug release profiles on targeted sites, being the assessment of their biocompatibility and safety a critical point of the process. The objective of this work was to characterize the cellular interactions and the potential toxicity of the novel developed polymeric nanoparticles (NPs), using human osteoblasts. For this purpose, Poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL 100 (PMMA-Eud, 50:50) NPs were produced and their physicochemical properties were characterized. The safety evaluation of both NPs was conducted through the characterization of cellular uptake (fluorescence microscopy), cyto- and genotoxicity (MTT, Comet and Micronucleus assays) using both normal and differentiated osteoblast cell line (MG-63-ATCC®CRL-1427™). The results confirmed the successful uptake of PMMA and PMMA-Eud by the cells. Both NPs were not cytotoxic in differentiated cells, although a moderate toxicity was detected in undifferentiated cells. As to their genotoxic potential, NPs induced primary DNA damage in osteoblasts, especially under a short-term exposure. Noteworthy, none of the NPs caused chromosome breaks, indicating that the primary DNA lesions were not converted into permanent genetic damage. On the other hand, an increased cell proliferative capacity was noted for PMMA-NPs, which deserves further investigation. In conclusion, the safety assessment of the two NPs indicated that both are biocompatible but display a weak genotoxicity that should be explored in other in vitro endpoints, e.g., gene mutation, and in vivo studies. Moreover, understanding how physicochemical features relate to toxicity will support the design of safer formulations for biomedical purposes.pt_PT
dc.description.sponsorshipFundação para a Ciência e Tecnologia (projects: EXCL/CTM-NAN/0166/2012, Pest-UID/DTP/04138/2013, ToxOmics, UID/BIM/00009/2013).pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/4786
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectGenotoxicidade Ambientalpt_PT
dc.subjectNanocarrierspt_PT
dc.subjectPMMA and PMMA-Eudpt_PT
dc.subjectHuman Osteoblastspt_PT
dc.subjectBiosafety Assessmentpt_PT
dc.subjectNanotoxicologypt_PT
dc.titleSafety evaluation of novel polymeric nanocarriers for drug delivery using human osteoblastspt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXCL%2FCTM-NAN%2F0166%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FDTP%2F04138%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F00009%2F2013/PT
oaire.citation.conferencePlaceLisboa, Portugalpt_PT
oaire.citation.title2.º Dia do Jovem Investigador do Instituto Nacional de Saúde Doutor Ricardo Jorge, INSA, 8 maio 2017pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isProjectOfPublication3b03b44b-4527-44bd-a501-a255c86d92f1
relation.isProjectOfPublication8b7dc2e1-c04d-4a11-8fa9-83ead9d8f256
relation.isProjectOfPublicatione9cc9728-4f09-4e3a-b30d-53d4429986fb
relation.isProjectOfPublication.latestForDiscovery3b03b44b-4527-44bd-a501-a255c86d92f1

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