Amphiphilic Macromolecular Drug Of Podophyllotoxin:synthesis?self-assembly And Studies In Vitro

Tumor is a major threat to human health and the chemotherapy has been successful in the treatment of tumor.Topoisomerases(Topos)are a well-validated target for anticancer therapy.Podophyllotoxin is the traditional DNA topoisomerase ?(Topo ?)inhibitor which shows high antitumor activity,but the serious side effects greatly limited its clinical application.Within the nucleus,DNA Topo ? solves the topological problems of DNA via a DNA breakage reunion mechanism to facilitate replication,transcription,recombination,chromosome condensation and decondensation.Etoposide and teniposide are semisynthetic derivatives of the natural podophyllotoxin and inhibit activity of Topo ? and are currently used clinically against various cancers,including small-cell lung cancer,testicular carcinoma,lymphoma,and Kaposi's sarcoma.However,They still have several limitations such as myelos'uppression and severe gastrointestinal disturbances and development of drug resistance promoted people to search for new derivatives of podophyllotoxin metabolic inactivation.So researchers are trying to find other new derivatives of podophyllotoxin that could overcome such deficiencies.The continuous development of new durg delivery systems is driven by the need to maximize therapeutic activity while minimizing negative side effcts.In order to improve the specific delivery of-durgs several durg carriers such as liposomes,micorparticles,naoa-associates,nanoparticle,durg polymer conjugates and polymeric micelles,have been developed.In recent years,amphiPhilic block copolymers consisting of hydrophilic and hydrophobic segment have attracted much attention because of their unique phase behavior in aqueous media and potential applications as durg delivery systems.Core-shell type nanoparticles or polymeric licelles can be formed through self-assembly of maphiphilic copolymers in aqueous environments.Nanoparticles as drug carriers can solubilize poorly water-soluble durgs in their inner core,avoid being quickly taken up by the retieuloendothelial system(RES)and prolong circulation time in the blood.Drug-loaded nano particles can also passively tgaret durgs to specific sites and reduce side effets.In this paper,the existing domestic and international research results and the structural characteristics of-podophyllotoxin in the structure-activity relationship of podophyllotoxin on the basis of the structural modification of podophyllotoxin and get the new structure.The paper is divided into five parts,the first chapter introduces the research progress of nano-formulations for podophyllotoxin,including liposomes,solid lipid nanoparticles,micelles,layered double hydroxides and microemulsion discussed,as a basis for research work.The second chapter is a synthesis of podophyllotoxin amphiphilic macromolecules and some characterization.The third chapter is a self-assembled micelles of PPG and it's nature study.The mean diameters was 181.6 nm,PDI was 0.132 and the zeta potential was-13.9 mV.The CMC of PPG micelles were calculated to be 1.6 ?g/mL.The fourth chapter is release studies in vitro of the PPG micelles.For PPG micelles in pH 2.0,it took 72 h to reach the maximum release of drug and there was no obvious burst effect of drug releasing.As for PPG micelles in pH 2.0 and pH 5.5,about 28.6%and 24.1%of drug was released over a period of 72 h.In comparison,79.5%of drug was released quickly from POD original drug suspension within 12h.The fifth chapter is inhibition of cell growth of human cervical cancer in vitro of the PPG micelles.