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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Carbohydrate Polymers; v. 216, p. 332-342, JUL 15 2019.
Web of Science Citations: 3
Abstract

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)

FAPESP's process: 17/10331-5 - Nanocarriers for siRNA Delivery: Synthesis e Selection of Vectors for the Treatment of Inflammatory Diseases.
Grantee:Marcio José Tiera
Support type: Regular Research Grants
FAPESP's process: 15/05148-1 - Synthesis and characterization of bioresponsives nanodevices for site-targeted release of siRNA for treatment of rheumatoid arthritis
Grantee:Maicon Segalla Petrônio
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia
Grantee:Sang Won Han
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/24259-0 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells
Grantee:Marcia Perez dos Santos Cabrera
Support type: Research Grants - Young Investigators Grants