Synthesis Of Polycarbonate And Their Application In Drug Delivery

Biomedical polymer materials,involved various aspects such as chemistry,physics,biology, medicine,are closely linked with our life.However,most biomedical polymer materials are faced with such problems as toxicity and degradation.Polycarbonate were widely used as drug release carrier due to theirs biocompatibility and biodegradability.The stimuli-responsive drug delivery system can achieve drug delivery by external stimuli or changes in internal pathological environments such as pH,redox,light,temperature,and enzymes.In this thesis,a kind of polycarbonate polymer material which is easy to synthesize and has uniform molecular weight distribution is designed and synthesized.At the same time,a reducing responsive camptothecin nano drug is prepared,as follows:In the first part,we designed and synthesized a 5-membered cyclic carbonate monomer 5-alkyneoxy-trimethylene carbonate(PTMC)containing an alkyne group.PTMC is homopolymerized or copolymerized with other compounds such as caprolactone and 5,5-dimethyltrimethylene carbonate to prepare a series of degradable polymers PPTMC,P(PTMC-co-CL),P(PTMC)-co-DTC).These polymers were characterized by ~1H NMR and GPC.The 5-propargyloxy-trimethylene carbonate(PTMC)monomer synthesized by the method is easy to prepare and has high yield,simple polymerization process and easy operation;and the obtained polymer has controllable molecular weight and degradable property.In the second part,we designed and developed a novel reductive cleavable polymer-camptothecin prodrug mPEG-b-PPTMC-g-CPT in which the polymer backbone consists of biodegradable diblock polycarbonate(mPEG-b-PPTMC).The side chain alkyne of PTMC is linked to the modified CPT by the Cu(I)-catalyzed azide-alkyne cycloaddition"click"reaction to obtain the polymer prodrug mPEG-b-PPTMC-g-CPT.The chemical structure of the mPEG-b-PPTMC and mPEG-b-PPTMC-g-CPT was characterized by ~1H NMR,the molecular weight and molecular weight distribution were measured by gel permeation chromatography(GPC).The particle size of the prodrug micelles was investigated by dynamic light scattering(DLS)and transmission electron microscopy(TEM)analysis.In vitro drug release studies indicate CPT in prodrug micelles is released in a reducing sensitivity environment.CLSM and MTT assays indicate that prodrug micelles can efficiently release CPT into Hela cells and inhibit cell proliferation.