Impact of Degree of Ionization and PEGylation on the Stability of Nanoparticles of Chitosan Derivatives at Physiological Conditions

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversité de Montréal-Canada-
Autor(es): dc.creatorMartinez Junior, André Miguel-
Autor(es): dc.creatorLima, Aline Margarete Furuyama-
Autor(es): dc.creatorMartins, Grazieli Olinda-
Autor(es): dc.creatorTiera, Vera Aparecida de Oliveira-
Autor(es): dc.creatorBenderdour, Mohamed-
Autor(es): dc.creatorFernandes, Julio Cesar-
Autor(es): dc.creatorTiera, Marcio José-
Data de aceite: dc.date.accessioned2025-08-21T19:26:54Z-
Data de disponibilização: dc.date.available2025-08-21T19:26:54Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-08-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/md20080476-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/241629-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/241629-
Descrição: dc.descriptionNowadays, the therapeutic efficiency of small interfering RNAs (siRNA) is still limited by the efficiency of gene therapy vectors capable of carrying them inside the target cells. In this study, siRNA nanocarriers based on low molecular weight chitosan grafted with increasing proportions (5 to 55%) of diisopropylethylamine (DIPEA) groups were developed, which allowed precise control of the degree of ionization of the polycations at pH 7.4. This approach made obtaining siRNA nanocarriers with small sizes (100–200 nm), positive surface charge and enhanced colloidal stability (up to 24 h) at physiological conditions of pH (7.4) and ionic strength (150 mmol L−1) possible. Moreover, the PEGylation improved the stability of the nanoparticles, which maintained their colloidal stability and nanometric sizes even in an albumin-containing medium. The chitosan-derivatives displayed non-cytotoxic effects in both fibroblasts (NIH/3T3) and macrophages (RAW 264.7) at high N/P ratios and polymer concentrations (up to 0.5 g L−1). Confocal microscopy showed a successful uptake of nanocarriers by RAW 264.7 macrophages and a promising ability to silence green fluorescent protein (GFP) in HeLa cells. These results were confirmed by a high level of tumor necrosis factor-α (TNFα) knockdown (higher than 60%) in LPS-stimulated macrophages treated with the siRNA-loaded nanoparticles even in the FBS-containing medium, findings that reveal a good correlation between the degree of ionization of the polycations and the physicochemical properties of nanocarriers. Overall, this study provides an approach to enhance siRNA condensation by chitosan-based carriers and highlights the potential of these nanocarriers for in vivo studies.-
Descrição: dc.descriptionDepartment of Chemistry and Environmental Sciences IBILCE São Paulo State University—UNESP, SP-
Descrição: dc.descriptionOrthopedic Research Laboratory Hôpital du Sacré-Coeur de Montréal Université de Montréal-Canada-
Descrição: dc.descriptionDepartment of Chemistry and Environmental Sciences IBILCE São Paulo State University—UNESP, SP-
Idioma: dc.languageen-
Relação: dc.relationMarine Drugs-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectDIPEA-
Palavras-chave: dc.subjectgene therapy-
Palavras-chave: dc.subjectnanoparticles-
Palavras-chave: dc.subjectphysiological pH-
Palavras-chave: dc.subjectsiRNA-
Título: dc.titleImpact of Degree of Ionization and PEGylation on the Stability of Nanoparticles of Chitosan Derivatives at Physiological Conditions-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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