Cubossoma funcionalizado com biopolímeros: desenvolvimento como carreador do anticancerígeno epirrubicina
Data
2023-12-08
Autores
Pimenta, Bárbara Vilela 
Orientadores
Mertins, Omar
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Desenvolvimento de cubossomas funcionalizados com biopolímeros, com
propriedades pH-responsivas, como material para encapsular e transportar
epirrubicina, visando a futura aplicação pela via oral. Metodologia: Para a produção
dos cubossomas, foram utilizados a monooleína e o surfactante Pluronic F127, além
de quitosana-N-arginina e o alginato. Adicionou-se também epirrubicina em solução
de etanol. As partículas foram produzidas e dispersas em dois valores de pH (2,5 e
7,4). As dispersões foram estudadas quanto ao seu tamanho e carga de superfície;
também foi avaliada a interação entre os cubossomas com e sem polímeros e a
albumina sérica bovina. As análises foram feitas empregando-se técnicas de
espalhamento de luz e potencial zeta, calorimetria por titulação isotérmica e
calorimetria diferencial de varredura. Os estudos sobre a estrutura cristalina das
partículas foram feitos utilizando crio-microscopia eletrônica de transmissão
(cryo-TEM) e espalhamento de raio-X a baixo ângulo (SAXS). Então, foram
realizados experimentos para determinação do encapsulamento e liberação de
fármaco, empregando-se o método de diálise. Resultados: A adição dos
biopolímeros alterou os valores de potencial zeta das partículas em ambas as
condições de pH estudadas; o tamanho dos cubossomas também sofreu alteração
após a incorporação dos polímeros, especialmente em pH 7,4. A interação
termodinâmica entre os cubossomas funcionalizados e a albumina foi efetiva e
modulada pelo pH, e também proporcionou um aumento na estabilidade térmica da
proteína, evidenciada pelo aumento em sua temperatura de transição. As análises
da estrutura interna evidenciaram uma transição parcial de fase cubica cristalina na
presença do fármaco em pH 7,4. O percentual de encapsulamento de epirrubicina foi
de 86% e o perfil de liberação determinado mostrou liberação prolongada do
fármaco, sugerindo um potencial aplicativo das nanopartículas. Conclusão: As
análises físico-químicas evidenciaram o efeito pH-responsivo dos cubossomas
funcionalizados com biopolímeros, que conduziram à mudanças no tamanho e carga
de superfície. A interação entre os cubossomas e a albumina também ocorreu
efetivamente, tanto em pH 2,5 quanto em 7,4, graças ao perfil de carga inerente aos
biopolímeros. As análises da estrutura cristalina indicaram simetria cúbica, com
transição de fase em pH 7,4, na presença de epirrubicina. A porcentagem de
encapsulamento e o perfil de liberação do fármaco evidenciaram a potencialidade de
aplicação dos cubossomas funcionalizados como sistemas drug delivery a serem
administrados em via oral.
Objective: Development of cubosomes functionalized with biopolymers, with pH-responsive properties, as a material to encapsulate and carry epirubicin for future applications via oral administration. Methodology: To produce the cubosomes, monoolein and Pluronic F127 surfactant were used, in addition chitosan-N-arginine and alginate. Epirubicin was also added in an ethanol solution and samples were produced and dispersed in two pH values (2.5 and 7.4). The dispersions were studied for their size and surface charge. The interaction between cubosomes with and without biopolymers and bovine serum albumin was evaluated. Analyses were performed using light scattering, zeta potential, isothermal titration calorimetry, and differential scanning calorimetry. Studies about the crystalline structure of the particles were conducted using cryo-electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). Encapsulation and drug release experiments were performed using the dialysis method. Results: The addition of biopolymers changed the zeta potential values of the particles at both studied pH conditions. The size of the cubosomes also changed after the incorporation of polymers, especially at pH 7.4. The thermodynamic interaction between the functionalized cubosomes and albumin was effective and pH modulated, and it increased the thermal stability of the protein, as evidenced by an increase in its transition temperature. The analysis of the particles internal crystalline structure unveiled a partial cubic phase transition in presence of the anticancer drug at pH 7.4. The percentage of epirubicin encapsulation was 86%, and the determined release profile showed prolonged release of the drug, suggesting the potential application of these nanoparticles. Conclusion: The physicochemical analyses evidenced the pH-responsive effect of cubosomes functionalized with biopolymers, leading to changes in size and surface charge. The interaction between functionalized cubosomes and albumin was effective at both pH 2.5 and 7.4, thanks to the inherent charge profile of the biopolymers. Analyses of the crystalline structure evidenced cubic symmetry with a partial phase transition at pH 7.4 in the presence of epirubicin. The percentage of encapsulation and the drug release profile demonstrated the potential application of functionalized cubosomes as oral drug delivery systems.
Objective: Development of cubosomes functionalized with biopolymers, with pH-responsive properties, as a material to encapsulate and carry epirubicin for future applications via oral administration. Methodology: To produce the cubosomes, monoolein and Pluronic F127 surfactant were used, in addition chitosan-N-arginine and alginate. Epirubicin was also added in an ethanol solution and samples were produced and dispersed in two pH values (2.5 and 7.4). The dispersions were studied for their size and surface charge. The interaction between cubosomes with and without biopolymers and bovine serum albumin was evaluated. Analyses were performed using light scattering, zeta potential, isothermal titration calorimetry, and differential scanning calorimetry. Studies about the crystalline structure of the particles were conducted using cryo-electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). Encapsulation and drug release experiments were performed using the dialysis method. Results: The addition of biopolymers changed the zeta potential values of the particles at both studied pH conditions. The size of the cubosomes also changed after the incorporation of polymers, especially at pH 7.4. The thermodynamic interaction between the functionalized cubosomes and albumin was effective and pH modulated, and it increased the thermal stability of the protein, as evidenced by an increase in its transition temperature. The analysis of the particles internal crystalline structure unveiled a partial cubic phase transition in presence of the anticancer drug at pH 7.4. The percentage of epirubicin encapsulation was 86%, and the determined release profile showed prolonged release of the drug, suggesting the potential application of these nanoparticles. Conclusion: The physicochemical analyses evidenced the pH-responsive effect of cubosomes functionalized with biopolymers, leading to changes in size and surface charge. The interaction between functionalized cubosomes and albumin was effective at both pH 2.5 and 7.4, thanks to the inherent charge profile of the biopolymers. Analyses of the crystalline structure evidenced cubic symmetry with a partial phase transition at pH 7.4 in the presence of epirubicin. The percentage of encapsulation and the drug release profile demonstrated the potential application of functionalized cubosomes as oral drug delivery systems.
Descrição
Citação
PIMENTA, Bárbara Vilela. Cubossoma funcionalizado com biopolímeros: desenvolvimento como carreador do anticancerígeno epirrubicina. 2023. 61 f. Dissertação (Mestrado em Biologia Molecular) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2023.