Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/185277
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dc.contributor.authorMuntimadugu, Eameema-
dc.contributor.authorSilva Abreu, Marcelle-
dc.contributor.authorVives, Guillem-
dc.contributor.authorLoeck, Maximilian-
dc.contributor.authorPham, Vy-
dc.contributor.authorMoral, Maria del-
dc.contributor.authorSolomon, Melani-
dc.contributor.authorMuro, Silvia-
dc.date.accessioned2022-05-02T14:07:57Z-
dc.date.available2022-05-02T14:07:57Z-
dc.date.issued2022-04-06-
dc.identifier.issn1422-0067-
dc.identifier.urihttp://hdl.handle.net/2445/185277-
dc.description.abstractPoly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) enhance the delivery of therapeutic enzymes for replacement therapy of lysosomal storage disorders. Previous studies examined NPs encapsulating or coated with enzymes, but these formulations have never been compared. We examined this using hyaluronidase (HAse), deficient in mucopolysaccharidosis IX, and acid sphingomyelinase (ASM), deficient in types A–B Niemann–Pick disease. Initial screening of size, PDI, ζ potential, and loading resulted in the selection of the Lactel II co-polymer vs. Lactel I or Resomer, and Pluronic F68 surfactant vs. PVA or DMAB. Enzyme input and addition of carrier protein were evaluated, rendering NPs having, e.g., 181 nm diameter, 0.15 PDI, −36 mV ζ potential, and 538 HAse molecules encapsulated per NP. Similar NPs were coated with enzyme, which reduced loading (e.g., 292 HAse molecules/NP). NPs were coated with targeting antibodies (> 122 molecules/NP), lyophilized for storage without alterations, and acceptably stable at physiological conditions. NPs were internalized, trafficked to lysosomes, released active enzyme at lysosomal conditions, and targeted both peripheral organs and the brain after i.v. administration in mice. While both formulations enhanced enzyme delivery compared to free enzyme, encapsulating NPs surpassed coated counterparts (18.4- vs. 4.3-fold enhancement in cells and 6.2- vs. 3-fold enhancement in brains), providing guidance for future applications.ca
dc.format.extent22 p.-
dc.format.mimetypeapplication/pdf-
dc.language.isoengca
dc.publisherMDPIca
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.3390/ijms23074034-
dc.relation.ispartofInternational Journal Of Molecular Sciences, 2022, vol. 23-
dc.relation.urihttps://doi.org/10.3390/ijms23074034-
dc.rightscc by (c) Muntimadugu, Eameema et al, 2022-
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.sourceArticles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))-
dc.subject.classificationLisosomes-
dc.subject.classificationNanopartícules-
dc.subject.otherLysosomes-
dc.subject.otherNanoparticles-
dc.titleComparison between Nanoparticle Encapsulation and Surface Loading for Lysosomal Enzyme Replacement Therapyca
dc.typeinfo:eu-repo/semantics/articleca
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.date.updated2022-05-02T13:29:33Z-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca
dc.identifier.idimarina6548040-
dc.identifier.pmid35409394-
Appears in Collections:Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

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