Desenvolvimento de sílicas mesoporosas para a liberação controlada e prolongada de fármacos

• Autor(a) principal: Costa, Marcela Bloise [UNIFESP]
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3649663; https://repositorio.unifesp.br/handle/11600/47281
• topic: Mesoporous silica; Controlled release; MCM-41; Ibuprofen; Covalent bond formation; Sílica-mesoporosa; Liberação controlada; MCM-41; Ibuprofeno; Formação de ligação covalente

Ordered mesoporous silicas has been considered one of the most promising inorganic systems to transport and control / sustain the release of drugs aiming to provide enhanced efficiency and reduced side effects in treatments of diseases like cancer. In this context, the present study had as main objective the production of systems for controlled and sustained release of drugs using the mesoporous silica MCM-41. Different types of chemical modification were produced in the inorganic matrix in order to enable the ibuprofen immobilization that is an anti inflammatory drug used as model in this study. MCM-41 modified with alkyl groups, such as MCM-41 mesophase, which has pores filled by cetyltrimethylamonium cation and C16-MCM-41, a structure which is not yet described in literature, prepared by co-condensation of hexadecyltrimetoxysilane on the silica walls, was used for the ibuprofen immobilization by adsorption as studied as sustained release systems. Controlled release systems were created by immobilization of ibuprofen in MCM-41 by covalent ester and amide bonds. These bonds can be broken by pH change or by enzymes action. These are possible external stimuli to control the drug release. The ester bond was formed by the reaction of ibuprofen carboxylic acid group with the epoxy ring of the glycidyloxipropyl group anchored to the surface of MCM-41, or by coupling of ibuprofen to glycidyloxipropiltrimetoxysilane and subsequent post-functionalization of MCM-41. The amide bond formation ibuprofen was produced by the reaction of amino groups of an APTES grafted silica with the carboxylic acid residue of ibuprofen by using the coupling agents EDC/NHS. The materials prepared and the intermediaries were previously characterized to confirm the immobilization of the drug as it was proposed. The release process of ibuprofen immobilized by adsorption on the MCM-41, C16-MCM-41 and MCM-41mesof matrices was performed in simulated body fluid and the results showed that the release profile was slower for the inorganic matrices with pores modified with alkyl chains when compared to the MCM-41 with empty pores. C16-MCM-41 showed a more prolonged release process, releasing about 10% of the ibuprofen immobilized after 300 minutes, while MCM-41 released about 25% of the drug after the same period. The mathematical model that best fit the release curves was Higuchi?s, indicating that the rate-limiting step of the process is the drug diffusion through the pores of the materials. For materials containing ibuprofen immobilized by ester bond the release tests were performed in phosphate buffer solution pH 6,6; 7,0 and 7,4. The drug release occurred at any pH , but it was slower in acid pH, yet relying on the influence of the lower solubility of ibuprofen in this condition. Considering the higher pH condition, where ibuprofen is more soluble, the slower release process was observed in the matrix produced by post-functionalization with pre-modified silane with ibuprofen. This material released about 5% of the immobilized drug after 300 minutes e the mathematical model that best fit the release curves was Kormeyer-Peppas?, indicating that although there is the additional contribution of the breaking the covalent bond, the process continues to be dominated by diffusion of the drug throught the pores. This work demonstrated the synthesis of a novel mesoporous silica matrix containing alkyl chains with 16 carbon atoms covalently attached to the silica walls, and different ways to control and prolong the release of ibuprofen. Besides that, the procedure developed for the immobilization of ibuprofen by covalent bonding should work for other types of drugs that containing carboxylic acid groups in the molecular structure.