| Texto completo | |
| Autor(es): |
Garcia, Bianca B. M.
;
Mertins, Omar
;
da Silva, Emerson R.
;
Han, Sang W.
Número total de Autores: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 92, p. 10-pg., 2024-01-25. |
| Resumo | |
The exploration of lipid-biopolymer hybrid systems has opened new avenues for enhancing nucleic acid delivery in gene therapy. Chitosan-N-arginine (CSA), due to its increased hydrophilicity and intracellular penetration resulting from arginine conjugation, holds promise in such formulations. Despite significant advances in developing novel hybrid systems, the influence of the degree of substitution (DS) in CSA on lipid-CSA hybrid systems (chitosomes) and their complexation with pDNA remains unclear. This study aimed to fill this knowledge gap by examining how the DS in CSA influences chitosome formation and function. We synthesized two CSA variants with different DSs and subsequently produced chitosomes to assess their physicochemical properties and transfection potential. The ligation of arginine to chitosan in CSA preparations was confirmed by FTIR and H1NMR spectroscopy, whereas elemental analysis indicated the DS at 5.7 % (CSA-6) and 3.4 % (CSA-3). Long-term stability was assessed in aqueous dispersions under storage temperatures of 25 degrees C or 4 degrees C, and we observed that CSA-3 and CSA-6 maintained their integrity for 11 and 12 months, respectively. Both chitosomes were successfully complexed with pDNA with the assistance of electrostatic interactions. Thermodynamic parameters indicated an exothermic interaction and a major contribution from the entropy change. Moreover, the chitosomes could protect pDNA from nucleases for 24 h, and the transfection efficiency in HeLa cells reached 21 %. Our findings suggest that while the DS in CSA influences pDNA complexation and compaction, it is not a determinant of the transfection efficiency. These findings will help in the design of improved hybrid nanosystems based on lipids and chitosan derivatives for nucleic acid delivery. (AU) | |
| Processo FAPESP: | 20/06913-1 - Desenvolvimento de nanopartículas de quitossomas para modulação da inflamação e angiogênese por dual delivery: uma abordagem para a terapia gênica para isquemia de membros |
| Beneficiário: | Bianca Bonetto Moreno Garcia |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 21/00971-2 - Nano cubossoma de fase cristalina e funcionalizado com biopolímeros: desenvolvimento como carreador de fármaco e estudos in vivo em zebrafish (Danio rerio) |
| Beneficiário: | Omar Mertins |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| 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 |
| Beneficiário: | Sang Won Han |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 22/04361-7 - Desenvolvimento de quitossomas para delivery de mRNA a células NK |
| Beneficiário: | Bianca Bonetto Moreno Garcia |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |
| Processo FAPESP: | 23/03903-3 - Investigação do papel da ANXA1 na recuperação da isquemia de membro e desenvolvimento de terapia gênica com vetores não virais |
| Beneficiário: | Sang Won Han |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |