| Texto completo | |
| Autor(es): |
Nunes, Renan S.
;
Cinel, Victor D. P.
;
Pieretti, Joana C.
;
Mariano, Kelli C. F.
;
dos Reis, Roberta A.
;
Halfeld, Morgana
;
Seabra, Amedea B.
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | NANOSCALE; v. 17, n. 21, p. 17-pg., 2025-05-08. |
| Resumo | |
Nitric oxide (NO) is a critical signaling molecule with significant therapeutic potential for biomedical applications, particularly in wound healing, antimicrobial activity, and tissue repair. However, its clinical translation is hindered by its instability and rapid degradation in biological environments. In this study, we employed chemometric techniques to optimize the synthesis of glutathione-loaded chitosan nanoparticles (GSH-CSNPs) produced via ionotropic gelation. GSH serves as a precursor molecule for S-nitrosoglutathione (GSNO), a key NO donor. A multivariate experimental design was applied to systematically investigate eight synthesis parameters, optimizing particle size, polydispersity index (PDI), zeta potential (ZP), stability, storage conditions, and NO release kinetics. The optimized nanoparticles exhibited a hydrodynamic diameter of 77.1 +/- 1.5 nm, a PDI of 0.209 +/- 0.010, and a ZP of +15.3 +/- 2.1 mV, ensuring considerable colloidal stability for at least 60 days at room temperature. NO release kinetics demonstrated a sustained and controlled release profile from GSNO-CSNPs compared to free GSNO, enhancing NO availability. Franz permeation cell assays revealed efficient GSNO permeation through synthetic skin membranes, and in vitro cytotoxicity assays using human fibroblast cells confirmed the biocompatibility of GSNO-CSNPs up to a NO donor concentration of 250 mu mol L-1. Additionally, S-nitrosylated protein quantification in FN1 cells showed that GSNO-CSNPs at 500 mu M induced a significant increase in S-nitrosylation levels, approximately 3 fold-higher than free GSNO at the same concentration, without a corresponding increase in cytotoxicity. This suggests that CSNPs enhance intracellular GSNO delivery, facilitating protein S-nitrosylation while maintaining cell viability. These findings highlight the pivotal role of Design of Experiments (DoE)-driven optimization in fine-tuning nanoparticle properties, providing a deeper understanding of how synthesis parameters influence their characteristics, and ultimately enhancing NO delivery systems for biomedical applications, particularly in skin-related therapies. (AU) | |
| Processo FAPESP: | 22/14645-2 - Hidrogéis e próteses vasculares liberadores de óxido nítrico para aplicações cardiovasculares |
| Beneficiário: | Marcelo Ganzarolli de Oliveira |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 24/04079-5 - Biomateriais nanocompósitos para liberação sustentada de óxido nítrico: modelagem e otimização de plataformas personalizadas visando aplicações biomédicas |
| Beneficiário: | Renan da Silva Nunes |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 24/20778-0 - Biomateriais à base de alginato para a administração de óxido nítrico |
| Beneficiário: | Morgana Halfeld Andrade |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 20/03646-2 - Impacto das nanoplataformas baseadas em óxido nítrico e quimioterápicos na citotoxicidade e sensibilização de células tumorais resistentes |
| Beneficiário: | Joana Claudio Pieretti |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 23/16363-7 - Duo- gasotransmissores para aplicações biomédicas: bioformulação de nanopartículas contendo Aspirina-NOSH |
| Beneficiário: | Roberta Albino dos Reis |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 24/12112-2 - Nanopartículas aliadas a transmissores gasosos para aplicações biomédicas e agrícolas |
| Beneficiário: | Amedea Barozzi Seabra |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |