(752g) Hollow Stimuli-Responsive Magnetic Silica Microparticles for Controlled Release and MRI Imaging

The possibility to control the release of active substances represents one of the most important attributes of targeted drug delivery (TDD). Here we are presenting one of the possible means for such delivery, which could be provided by microscopic, synthetically created particles from composite material based on silica, thermoresponsive polymer poly-N-isopropylacrylamide (PNIPAM, LCST 32°C) and magnetite nanoparticles. All of the materials mentioned above provide desired microparticles with unique characteristics such as endurance and hardness of silica, the ability of thermoresponsive polymers to change its volume in dependence on temperature and the possibility of induction heating as a result of the presence of magnetite nanoparticles. By combining these attributes, the final microparticles could act as a vessel for TDD able to transport the delivered substance into its destination and then release it there as a reaction to an external stimulus being the application of alternating magnetic field.

The synthesis of such microparticles consists of several steps. Firstly, it is essential to prepare macroporous hollow silica microparticles with incorporated magnetite nanoparticles using a solid template method. This is achieved by following a chain of reactions starting with the production of solid polystyrene (PS) template in the form of monodisperse spheres with relatively uniform size in the range of 1 mm. Then the silica/PS/Fe₃O₄ composite microparticles are obtained using modified Stober method based on the reactions of condensation and hydrolysis. During this process, Fe₃O₄ nanoparticles are gradually absorbed into the growing silica seeds, thus creating continuous composite silica/ Fe₃O₄  network on the surface of the PS templates. The last step, constituting of the PS core removal, is easily done by dissolving in toluene and leads to the creation of hollow silica/Fe₃O₄ microparticles with pores of the approximate size near 100 nm. In order to proceed to the final product being silica/PNIPAM/Fe₃O₄ hybrid microparticles, the already existing silica/Fe₃O₄ microparticles have to be functionalized by introducing the double bond onto its surface utilizing 3-(trimethoxysilyl)propyl methacrylate (3-MOP), allowing PNIPAM  to be subsequently attached onto the microparticles as a result of radical copolymerization of 3-MOP silica with NIPAM. The as prepared hybrid microparticles were characterized in terms of its composition and morphology. Additionally, also the possibility of radiofrequency heating and release process of a model substance (Nile Red) were investigated. Since it would be highly beneficial to be able to observe the behavior of microparticles containing magnetite in 3D surroundings, the method of MRI was used.