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In Silico and In Vitro Tailoring of a Chitosan Nanoformulation of a Human Metabolic Enzyme

2021-03-04Journal article Open access
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dc.contributor.authorLino, Paulo Roque
dc.contributor.authorLeandro, João
dc.contributor.authorAmaro, Mariana
dc.contributor.authorGonçalves, Lídia
dc.contributor.authorLeandro, Paula
dc.contributor.authorAlmeida, António José
dc.date.accessioned2023-09-14T11:59:52Z
dc.date.available2023-09-14T11:59:52Z
dc.date.issued2021-03-04
dc.date.updated2023-02-27T15:49:07Z
dc.description.abstractEnzyme nanoencapsulation holds an enormous potential to develop new therapeutic approaches to a large set of human pathologies including cancer, infectious diseases and inherited metabolic disorders. However, enzyme formulation has been limited by the need to maintain the catalytic function, which is governed by protein conformation. Herein we report the rational design of a delivery system based on chitosan for effective encapsulation of a functionally and structurally complex human metabolic enzyme through ionic gelation with tripolyphosphate. The rationale was to use a mild methodology to entrap the multimeric multidomain 200 kDa human phenylalanine hydroxylase (hPAH) in a polyol-like matrix that would allow an efficient maintenance of protein structure and function, avoiding formulation stress conditions. Through an in silico and in vitro based development, the particulate system was optimized with modulation of nanomaterials protonation status, polymer, counterion and protein ratios, taking into account particle size, polydispersity index, surface charge, particle yield production, protein free energy of folding, electrostatic surface potential, charge, encapsulation efficiency, loading capacity and transmission electron microscopy morphology. Evaluation of the thermal stability, substrate binding profile, relative enzymatic activity, and substrate activation ratio of the encapsulated hPAH suggests that the formulation procedure does not affect protein stability, allowing an effective maintenance of hPAH biological function. Hence, this study provides an important framework for an enzyme formulation process.pt_PT
dc.description.sponsorshipThis work was supported by FEDER and Fundação para a Ciência e a Tecnologia, I. P. through national funds: Projects UIDB/04138/2020 and UIDP/04138/2020, research projects PTDC/QUI/64023/2006 and PTDC/EBB-BIO/101237/2008 and grants SFRH/BSAB/1210/2011 (to A.J.A.) and SFRH/BD/47946/2008 (to P.R.L.). This work has also received funding from the National PKU Alliance, USA.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationLino PR, Leandro J, Amaro M, Gonçalves LMD, Leandro P, Almeida AJ. In Silico and In Vitro Tailoring of a Chitosan Nanoformulation of a Human Metabolic Enzyme. Pharmaceutics [Internet]. 2021 Mar 4;13(3):329. Available from: http://dx.doi.org/10.3390/pharmaceutics13030329pt_PT
dc.identifier.doi10.3390/pharmaceutics13030329pt_PT
dc.identifier.slugcv-prod-2420938
dc.identifier.urihttp://hdl.handle.net/10451/59290
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationResearch Institute for Medicines
dc.relationResearch Institute for Medicines
dc.relationNEW SRATEGIES FOR ANTIGEN AND PROTEIN DELIVERY USING NANOBIOMATERIALS
dc.relationTOWARDS A NEW APPROACH TO PHENYLKETONURIA TREATMENT: STABILISATION OF PHENYLALANINE HYDROXYLASE USING NANOBIOMATERIALS
dc.relation.publisherversionhttps://www.mdpi.com/1999-4923/13/3/329pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectchitosanpt_PT
dc.subjectmolecular modellingpt_PT
dc.subjectenzyme therapeuticspt_PT
dc.subjectself-assemblypt_PT
dc.subjectnanoencapsulationpt_PT
dc.subjecthuman phenylalanine hydroxylasept_PT
dc.titleIn Silico and In Vitro Tailoring of a Chitosan Nanoformulation of a Human Metabolic Enzymept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleNEW SRATEGIES FOR ANTIGEN AND PROTEIN DELIVERY USING NANOBIOMATERIALS
oaire.awardTitleTOWARDS A NEW APPROACH TO PHENYLKETONURIA TREATMENT: STABILISATION OF PHENYLALANINE HYDROXYLASE USING NANOBIOMATERIALS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FEBB-BIO%2F101237%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI%2F64023%2F2006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/PIDDAC/SFRH%2FBSAB%2F1210%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/PIDDAC/SFRH%2FBD%2F47946%2F2008/PT
oaire.citation.issue3pt_PT
oaire.citation.startPage329pt_PT
oaire.citation.titlePharmaceuticspt_PT
oaire.citation.volume13pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
oaire.fundingStreamPIDDAC
oaire.fundingStreamPIDDAC
person.familyNameLino
person.familyNameDiogo Gonçalves
person.familyNameLeandro
person.familyNameLeitão das Neves Almeida
person.givenNamePaulo
person.givenNameLídia Maria
person.givenNamePaula
person.givenNameAntónio José
person.identifierI-6590-2012
person.identifier.ciencia-id7211-22BA-86AD
person.identifier.ciencia-id1610-4815-076E
person.identifier.ciencia-id8312-F853-C47A
person.identifier.orcid0000-0003-4221-4499
person.identifier.orcid0000-0002-6799-2740
person.identifier.orcid0000-0002-2946-9342
person.identifier.orcid0000-0002-7807-4726
person.identifier.ridN-2179-2015
person.identifier.ridA-8323-2014
person.identifier.scopus-author-id56427809800
person.identifier.scopus-author-id6602522134
person.identifier.scopus-author-id57195052432
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.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
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.cv.cienciaid7211-22BA-86AD | Lídia Maria Diogo Gonçalves
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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