Amphipathic chitosans improve the physicochemical properties of siRNA-chitosan nanoparticles at physiological conditions

Autor(es)

Martins, Grazieli Olinda ^[1] ; Petronio, Maicon Segalla ^[1] ; Furuyama Lima, Aline Margarete ^[1] ; Martinez Junior, Andre Miguel ^[1] ; de Oliveira Tiera, Vera Aparecida ^[1] ; Calmon, Marilia de Freitas ^[2] ; Leite Vilamaior, Patricia Simone ^[2] ; Han, Sang Won ^[3] ; Tiera, Marcio Jose ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, IBILCE, Dept Chem & Environm Sci, Sao Jose Do Rio Preto, SP - Brazil

^[2] Sao Paulo State Univ UNESP, IBILCE, Dept Biol, Sao Jose Do Rio Preto, SP - Brazil

^[3] Univ Fed Sao Paulo, Paulista Sch Med, Dept Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Carbohydrate Polymers; v. 216, p. 332-342, JUL 15 2019.
• Citações Web of Science: 3

Resumo

Chitosan has received a lot of attention as a carrier for small interfering RNA (siRNA), due to its capacity for complexation and intracellular release of these molecules. However, one of its limitations is its insolubility at neutral pH and the tendency towards aggregation of its nanoparticles in isotonic ionic strength. In this study, a series of amphipathic chitosans were synthesized by varying the degree of acetylation (DA) from (similar to)2 to (similar to)30 mol% and the degree of substitution (DS) from 5 to 25%. by tertiary amino groups (DEAE) The results showed that the adjustment of these parameters decreases the interparticle interactions mediated by hydrogen bonding to obtain nanoparticles with improved colloidal stability. siRNA-containing nanoparticles of 100 to 150 nm with low polydispersities (0.15-0.2) and slightly positive zeta potentials ((similar to)+ 5 mV) were resistant to aggregation at pH 7.4 and ionic strength of 150 mM. This resistance to aggregation is provided by changes on the nanoparticle surface and highlights the importance of more organized self-assembly in providing colloidal stability at physiological conditions. Additionally, the PEGylation of the most promising vectors conferred favorable physicochemical properties to nanoparticles. The chitosans and their nanoparticles exhibited low toxicity and an efficient cell uptake, as probed by confocal microscopy of rhodamine labeled vectors. The results provide a new approach to overcome the limited stability of chitosan nanoparticles at physiological conditions and show the potential of these amphipathic chitosans as siRNA carriers. (AU)

• Processo FAPESP: 17/10331-5 - Nanocarreadores para a Liberação de siRNA : Síntese e seleção de vetores para o tratamento de doenças inflamatórias
• Beneficiário: Marcio José Tiera
• Modalidade de apoio: Auxílio à Pesquisa - Regular
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• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/05148-1 - Síntese e caracterização de nanodispositivos bioresponsivos para liberação sítio dirigida de siRNA para o tratamento da artrite reumatóide
• Beneficiário: Maicon Segalla Petrônio
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/20206-8 - Modulação de monócitos, macrófagos e pericitos pelos genes dos fatores estimuladores de colônia para tratamento de isquemia de membros em modelo murino
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• Modalidade de apoio: Auxílio à Pesquisa - Temático