Acilação da quitosana e da N,N,N-trimetilquitosana para aplicação potencial em diagnóstico e terapia gênica

Detalhes bibliográficos
Ano de defesa: 2015
Autor(a) principal: Joyce Cristina da Cruz Santos
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Minas Gerais
UFMG
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://hdl.handle.net/1843/BUBD-9ZRGYC
Resumo: This work shows the synthesis of chemically modified chitosan derivative with palmitoyl groups and derivatives of N, N, N-trimetilquitosana (TMC) modified with fatty acids of different acyl chain sizes (5, 10 and 18 carbons). TMC N-acylated derivatives were characterized and calculated the degree of chemical substitution using 1H NMR. The chemical modification of TMC acyl chains was performed for the purpose of prepare new nanoscale complexes were prepared (polyplexes) between the TMC and its derivatives and single-stranded oligonucleotides (ONs). The influence of the length of the hydrophobic chain (C5, C10 and C18) in the interaction of TMC with the ONs and polyplexes formation was studied and found that the size of the hydrophobic chain is an important factor in the interaction of the polymer with the ON and also stability the formed particle. The polyplexes prepared with TMC-SA2 (modified with stearyl groups) showed better results in cell transfection in HeLa cells, and greater oligonucleotide condensation capacity and high stability in cell culture medium. The results indicate that the size of the hydrophobic chain is important for the interaction of the polymer with the ON and indicate the existence of a balance of electrostatic/hydrophobic interactions between the polymer and the oligonucleotide. Resazurin cytotoxicity results show that, TMCs, and modified fatty acids, as well as those prepared polyplexes showed no cytotoxicity on HeLa cells. The influence of modification of chitosan with palmitoyl groups was studied by combination and stabilization of polymer with quantum dots (QDs). The results have evidenced that both chitosan and N-palmitoylchitosan have performed as capping ligands on nucleating and stabilizing colloidal CdS QDs with estimated average size below 3.5 nm and fluorescente activity in the visible range of the spectra.