Development of controlled drug delivery systems using uniform nanoporous materials as matrices

Abstract

This thesis reports the study of fine-tuning the properties of ordered mesoporous silicas and their potential application in controlled drug delivery systems for both small molecule model drug of ibuprofen (IBU) and large protein drug of bovine serum albumin (BSA). The release rate of IBU from SBA-15 functionalized by post synthesis is found to be effectively controlled due to the strong ionic interaction between carboxyl groups in IBU and amine groups on the surface of SBA-15. In the fabrication of controlled delivery system for BSA, the adsorption isotherms of BSA on SBA-15 were determined at various conditions and higher BSA adsorption capacities were obtained on SBA-15 with higher amine group content, larger pore size and near the isoelectric region of BSA. Electrostatic interaction is suggested to be the driving force that prompts mild BSA adsorption on hydrophilic surface of amine-functionalized SBA-15 and slower release rate on SBA-15 with higher amine group contents. Meanwhile, the conformational changes of BSA under various processing conditions were also investigated. Finally, a smart pH-controllable drug delivery system was successfully prepared through encapsulation of amine-functionalized SBA-15 with poly(acrylic acid) by electrostatic assembly. This novel drug delivery system is believed to have potential application in targeted oral delivery of therapeutic proteins, which can release drugs to the ideal site like small intestine or colon while protecting them from the acidic condition in the stomach.