Nanopartículas poliméricas doadoras de óxido nítrico para aplicações tópicas

• Ano de defesa: 2017
• Autor(a) principal: Pelegrino, Milena Trevisan [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Nitric oxide; Chitosan nanoparticles; S-nitrosothiols; Pluronic F-127; Controlled release; Óxido nítrico; Nanopartículas de quitosana; S-nitrosotióis; Luronic F-127; Liberação controlada
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5006596; http://repositorio.unifesp.br/handle/11600/49914

Nitric oxide (NO) is a lipophilic uncharged free radical with small size. These features, help NO to diffuse in biological medium by crossing physiological barriers and communicating with cells. NO is involved in several important physiological processes in mammal cells, such as, vasodilation, macrophage toxicity, antitumoral activity and wound healing. In plant cells, NO is involved in seed germination, resistance to abiotic and biotic stress and leaf senescence. In biological medium, NO has a half-life of 1-5 s, then, therapeutical application of NO requires molecules capable of increasing its half-life. The S-nitrosothiols (RSNOs) are a class of NO donors formed by the nitrosation of thiol-containing molecules. In addition, the RSNOs are spontaneously decomposed and release the NO, what increases the NO half-life. There is a great interest in developing materials capable of carry and release the NO to apply in biomedical and agricultural fields. The nanotechnology and RSNOs combined are a strategy to delivery NO and achieve its therapeutical application. In this study, chitosan nanoparticles (CS NPs) and hidrogel of Pluronic F-127 (PL) containing RSNOs were synthesized and characterized to evaluated their potential in biomedical and agricultural applications. The CS NPs were synthesized through ionotropic gelation using sodium tripolyphosphate (TPP) as counter-ion, thus, the chitosan nanoparticles (CS NPs) obtained has size of ca. 100.0 ± 0.2 nm, measured by dynamic and static light scattering (DLS and SLS). The CS NPs has positive zeta potential of +19.6 ± 0.5 mV, moderate polydispersity of 0.27 ± 0.03, and the CS NPs also incorporated with high efficiency (greater than 98%) the RSNOs, S-nitroso-mercaptosuccinic acid (S-nitroso-MSA) and S-nitrosoglutathione (GSNO). Sequentially, the CS NPs were incorporated into PL hydrogel, in order to formulate a semisolid material in physiological temperature which is desired for a topical application. In addition, ex vivo experiments showed that NO released from CS NPs can permeate the human skin and increase the NO stores in epidermis. Regarding the safety of the CS NPs, cytotoxicity essays were performed. The CS NPs do not cause significant toxicity to healthy cell line (Melan-A) and, in contrast the CS NPs cause toxicity in tumoral cell lines (B16F10, K562, HepG2, Lucena-1). The application of NO donors in corn plants (Zea Mays) and sugarcane (Saccharum spp) helped to mitigate the abiotic stress effects of high salinity and NO donors encapsulated in CS NPs have shown more pronounced effects and a sustainable NO release in vivo. Taken all together, the CS NPs are an interesting vehicle for biomedical and agriculture applications, highlighting dermatological usage and resistance against abiotic stress.