Híbridos de gel polimérico em sílica mesoporosa estruturalmente ordenada para liberação controlada de fármacos

• Ano de defesa: 2009
• Autor(a) principal: Andreza de Sousa
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: poli(N-isopropilacrilamida); híbridos orgânico-inorgânicos; atenolol; síntese; liberação controlada de fármacos; SBA-15; caracterização estrutural; Engenharia quimica
• Link de acesso: http://hdl.handle.net/1843/BUBD-8E5MCA

Ordered mesoporous materials are currently a field of intensive research activity due to their high potential in a very broad range of applications. Mesoporous materials like SBA-15 posses large surface areas (690-1040m2.g-1) and pores size ranging from 4.6 to 30nm and are considered a suitable material for hosting and further delivery a variety of molecules of pharmaceutical interest. Temperature-responsive hydrogels, such as poly(N-isopropylacrylamide) P(N-iPAAm), are a well-studied class of drug delivery systems, as they can respond pronouncedly to temperature changes. In water, P(N-iPAAm) exhibits phase transition at a lower critical solution temperature (LCST) of approximately 33C. Below the LCST, the hydrogel incorporates water and swells, whereas the release of water in response to an increase in temperature causes shrinkage. Therefore, the combination of the mesoporous material SBA-15 with the polymeric gel poli(N-isopropylacrylamide) can lead to the formation of a material with potential for application as new drug delivery systems, because self-regulated delivery allows for drug release when it is needed. In this work, we study the synthesis and characterization of hybrids consisting of the poly(N-isopropylacrylamide) hydrogel and SBA-15 to evaluate the applicability of this system as a matrix for controlled drug delivery. Hybrid materials were synthesized following two different routes named as Route 1 and Route 2. In Route 1 the inorganic portion was synthesized together the polymeric gel. The procedure adopted in Route 2 to incorporate the hydrogel into the SBA-15 network was monomer adsorption followed by in situ polymerization, with different ratios of polymer/silica. The materials were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Nitrogen Adsorption, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Small Angle X Ray Scattering (SAXS), X-Ray Photoelectron Spectroscopy (XPS), Nuclear Magnetic Resonance (RMN), Ultraviolet Visible Diffuse Reflectance Spectroscopy (UV-VIS-DRS) and Thermal Analysis. Through the FTIR analysis technique, it was possible to observe characteristic absorption bands of the silica vibrations, as well as absorption vibrations bands due the presence of polymeric material, suggesting the incorporation of P(N-iPAAm) into the silica structure. The presence of the atenolol in the mesoporous material and hybrids was also confirmed by FTIR. The thermal stability and the degradation of the polymer chains with and without drug were determined by thermogravimetry. The incorporation of the polymer phase into the mesoporous silica led to a significant change in the structural properties of the system, with the decrease of the specific surface area, pore size and pore volume. A symmetric reduction in hysteresis was observed after the formation of P(N-iPAAm) in the SBA-15 network, probably due to the presence of constrictions in the porous structure. It was observed a bimodal porosity in the pure and hybridssamples. For SBA-15, the bimodal porosity can be due to the presence of primary and secondary mesoporores. For hybrid samples, the bimodal porosity can be caused by the presence of the pores with constrictions. The adsorption isotherms obtained after atenolol incorporation into the pores of SBA-15 and [SBA-15/P(N-iPAAm)] still displayed a mesoporous characteristic. The results obtained by SEM, TEM and SAXS for the samples reveal a well-defined hexagonal arrangement of uniform mesoporous structure. The presence of hydrogel into the mesoporous silica structure was confirmed by RMN-MAS and UV-VIS. Atenolol was incorporated into the samples by soaking the sample disks into drug solution (10mg.mL-1). The amount of atenolol incorporeted in the pure sample and hybrids systems varies from 17 to 18% (m/m). A release assay with atenolol monitored by UV-VIS spectroscopy was performed for pure SBA-15 and a hybrid system at different temperatures in order to evaluate the influence of the thermosensitive behavior of the polymer on the release kinetics. The response of the hybrid system as a drug delivery device is influenced by the volumetric contraction of P(N-iPAAm) up to the lower critical solution temperature due to phase transition. Above the lower critical solution temperature (LCST), drug release depends essentially on the temperature. The above results are promising to evaluate the adsorption capacity and kinetics in drug delivery process from the porous structure of the hybrid system modulated by the incorporation of the polymeric gel.