Synthesis And Properties Of The Amphiphilic Block Copolymers With Poly (Ascorbyl Acrylate) As Hydrophilic Block For Drug Carrier

Vitamin C is a nutrient for human health. Its neuroprotective effects hasbeen found. And its penetration into the brain presented the molecularselectivity and physiological disposition between ascorbate andsodium-dependent vitamin C transporters SVCT2. These biochemicaldiscoveries exhibited the significance of ascorbate in the treatment of tumorsand central nervous disorders, meanwhile, also hinted that it might serve toimprove the specificity of overall drug delivery system to the pathologicalsites if ascorbate as a promising targeting molecule is used to modify drugcarriers. Polylactic acid is a biocompatible and biodegradable material. It hasbeen widely used in the field of medicine. In this thesis, a novel type ofamphiphilic block copolymers poly(lactic acid)-block-poly(ascorbyl acrylate)(PLA-block-PAAA) with biodegradable poly(lactic acid) as hydrophobicblock and poly(ascorbyl acrylate)(PAAA) as hydrophilic block wassuccessfully developed. The mainly work are as follows:1. We successfully synthesized amphiphilic block copolymers poly(lacticacid)-block-poly(ascorbyl acrylate)(PLA-block-PAAA) with differenthydrophobic-hydrophilic proportion by a combination of ring-openingpolymerization and atom transfer radical polymerization, followed byhydrogenation under normal pressure; 2. We systematicly studied the self-assembly behavior of the amphiphilicpolymers. We determined the optimum self-assembly method and got therelatively stable nanoparticle solution system. The self-assembly capability ofthe amphiphilic polymers were monitored by UV. The morphology and size ofthe nanocarriers via self-assembly were detected by DLS, TEM and CryoTEM.Results showed that these amphiphilic polymers self-assembled to formuniform spherical micellar aggregates with average size in the range of40-220nm and the CMC values of the copolymers were in the range of15.0and32.3mg/L;3. Cytotoxicity of the amphiphilic block copolymers were detected byMTT assay.We found that after culture cells72hours with PLA-block-PAAAand the control material MPEG-block-PLA, the cell survival rate can still bemaintained at about80%. The results proved that the materials are safe andnon-toxic, and it has the potential to be used as drug delivery carrier in vivo;4. A preliminary exploration of the materials targeting was monitored bythe fluorescent-probe technology. But we failed to prove that the targeting ofthe materials. We took some measures to adjust the materials, for exmaple,added T-20to auxiliary self-assembly and then the materials have nosignificant release behavior at the first30hours;5. Using Nile red as a kind of fluorescent molecular model drug, and westudied the release behavior of the materials. Combination the results of DLS,Zeta potential and the fluorescence monitoring results, we found that rapidrelease of the polymers in the neutral pH value was due to the hydrophilicblock PAAA destroyed by the ionic strength and dissolved oxygen in aqueoussolution.