Nanoparticles for multifunctional drug delivery systems

Multifunctional drug delivery systems incorporated with stimuli-sensitive drug release, magnetic nanoparticles and magnetic resonance (MR) T2 contrast agents is attracting increasing attention recently. In this thesis, works on polymer nanospheres response to temperature change, superparamagnetic iron oxide nanoparticles (SPION)/polymeric composite materials for MR imaging contrast agents are summarized. A “shell-in-shell” polymeric structure has been constructed through a “modified double-emulsion method”. Thermosensitive inner shell is comprised of poly(N-isopropylacrylamide) which undergoes phase transition at body temperature. Such a feature could facilitate drug release at an elevated temperature upon administration. Furthermore, the dual-shell structure is covered by a layer of gold nanoparticles. According to the cytotoxicity tests, the biocompatibility is shown to be enhanced due to the layer of gold. SPION have been prepared using a high temperature decomposition method. Particle growth of SPION is monitored by transmission electron microscope and synchrotron X-ray diffraction. Poly(L,L-lactide)@SPION (PLLA@SPION) composite particles have been prepared through surface-initiated ring-opening polymerization which has been developed in our lab. For biomedical applications, it is essential to transfer the particles to physiological solutions from organic solutions. Phase transfer of SPION has been carried out by utilizing small molecules. Stability at the neutral pH is of large concern for such transfer systems. A novel phase transfer agent, Pluronic F127 (PF127), a triblock copolymer has been applied and the stability of the aqueous PF127@oleic acid (OA)@SPION solution has been greatly enhanced over a broad pH range. Most interestingly, PF127@OA@SPION show remarkable efficacy as T2 contrast agents as indicated by relaxometric measurements compared with commercially available products.QC 2010111