Preparation Of Redox-sensitive Shell Cross-linked Carriers For Controlled Release Of Bioactive Agents

Nanocarriers obtained from self-assembly of amphiphilic block copolymers in aqueoussolution have been well investigated in the past decades. However, in the practical applications,the stability of nanocarriers is of great challenge since they would disassemble upon stimulationssuch as pH, temperature, etc. The core cross-linked or shell cross-linked approaches have beendeveloped to maintain their structural integrity. This dissertation mainly focuses on fabrication ofredox-sensitive shell cross-linked nanocarriers via (inverse) miniemulsion reversibleaddition-fragmentation chain transfer (RAFT) polymerization. This dissertation includes fourparts as following:1. Shell cross-linked poly(2-(dimethylamino) ethyl methacrylate)-b-polystyrene(PDMAEMA-b-PS) nanoparticles were prepared in a miniemulsion RAFT system, in whichPDMAEMA RAFT chain transfer agents acted as stabilizers. The amount of the cross-linker wasan influence parameter on the morphology. The diameter of nanoparticles increased with aconcomitant increasing in amount of the cross-linker. And the as-prepared shell cross-linkednanopartilces had an inherent fluorescent property. So they can be directly used as a drugdelivery carrier in vivo without any fluorescence labeling treatments.2. When the amount of cross-linker was relative low, the shell cross-linkedPDMAEMA-b-PS nanoparticles underwent a fission process during the miniemulsion RAFTpolymerization process. The fission was induced by the different rate between the monomertransfer and the polymerization in situ, along with the differences in thermal expansivity of themonomers and the PDMAEMA RAFT chain transfer agents.3. Shell cross-linked poly(2-(dimethylamino) ethyl methacrylate)-b-poly(methylacrylicacid)(PDMAEMA-b-PMAA) nanocapsules were prepared in an inverse miniemulsionRAFT system, in which PDMAEMA RAFT chain transfer agents acted as stabilizers. Theas-prepared nanocapsules had well definite core-shell structures and could be used as a carrier toencapsulate sodium chloride. The shell cross-linked nanocapsules can be degraded into diblockcopolymers after the addition of the redox-reagent dithiothreitol (DTT). 4. Shell cross-linked poly(2-(dimethylamino) ethyl methacrylate)-b-polystyrene(PDMAEMA-b-PS) nanoparticles were prepared via surfactant-free emulsion reversibleaddition-fragmentation chain transfer polymerization (SFE-RAFT), in which PDMAEMA RAFTchain transfer agents acted as stabilizers. The resultant nanoparticles had a well definite coreshell structure and could be used as a carrier to encapsulate of hydrophobic drugs indomethacin(IND). The drug release could be triggered by DTT and the release rate can be modulated by pH.Moreover, the shell cross-linked nanoparticles had a good biocompatibility. These propertiesindicated that these nanoparticles would be used as promising drug delivery vehicles.