Design and Synthesis of New Photodegradable Silicon-containing Poly(Lactic-co-glycolic Acid) with Applicability

• Main Authors: Chuang, Hung, 莊鴻
• Other Authors: Hwu, Jih-Ru
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/21279036208078209837

碩士 === 國立清華大學 === 化學系 === 101 === Drug delivery system has been investigated for several years. Several excellent drug candidates failed to be applied on clinical usage, as their high toxicity to both tumor and normal cells. Therefore, by using drug delivery system, the toxicity of these candidates could be neutralized, and potential new therapeutics could be developed. Furthermore, effective drug controlled release could be well manipulated by drug delivery system. In this thesis, we have developed a new concept to apply Norrish Type reaction on poly(lactic-co-glycolic acid) to produce a novel polymer for drug delivery and release. First, we used ethyl acetoacetate as starting materials and introduced silyl group on position of acetate. Second, to modify the monomer with the hydroxyl group, we treated ethyl -[(trimethylsilyl)methyl]acetoacetate with two kinds of bases and chloromethyl benzyl ether, then we used palladium to deprotect benzyl group under hydrogen and the following basic treatment to get the desired monomer. Furthermore, we carried out polymerization with lactide, glycolide and the designed monomer in 78% yield; the average molecular weight of polymeric product is about 24,000 Da, estimated by GPC. Finally, the photo treatment of designed polymer was performed with medium-pressure mercury UV lamp. After photo-irradiated induction, the synthesized polymer was cleaved into the fragments of molecular weight about 8,000 Da; the average numbers of bond broken is 1.8, and the efficiency of bond broken is 92.5%. This photo sensitivity of polymer can be modified to control the polymer cleavage, as well as to control and release the drug bound to the polymer. With the delivery of polymeric carrier, the cellular local density of drug concentration would be higher than delivery without any assistance. Also, the polymeric shielding could decrease the rate of metabolism of drug in the body and keep the drug concentration in the blood at the proper range.