Research On The Synthesis,Characteristic Of GA Derivative And Its Self-Assembly Drug Delivery System

Gambogic acid?GA?is organic lipid material by natural plant?gamboge?,which has the characterized of broad-spectrum anti-tumor activities.However,the defect of high toxicity,low solubility,poor selectivity and short half-value period,restrict its application in anti-cancer field.Therefore,for gambogic acid,it is necessary to improve its selectivity,reduce the toxicity,and prolong the half-value period in vivo.For the sake of solving these problems above,in this paper,we used GA as model drug to design and synthesis a new amphiphilic compound,that is,TSXG.In suitable dispersion medium,it has the ability to form a self-assemble micelle.And we had conduct a series of study to detected its behavior in vivo and in vitro.The content of the research include that the synthesis of TSXG,preparation and representation of TSXG self-assembly micelles,the stability of TSXG,research on the tissue distribution and pharmacokinetics of TSXG,study on pharmacodynamics of TSXG.The synthesis of TSXG:In this chapter,we used the method of structural modification to design and synthesis a amphiphilic compound,that is TSXG.Besides,we also adopted the method of TLC,HPLC/MS,NMR-H,IR to confirm its chemical construction.Preparation and representation of TSXG self-assembly micelles:In this chapter,we adopted the injection method of of ethyl alcohol and acetone.We also used laser particle size analyzer to confirm the average particle size of TSXG is 100 nm and the Zeta potential is about-30 mV indicated it possesses good stability.The stability of TSXG:In this chapter,we used physical experimental method to investigate the influence of different temperature on TSXG.Results show that it is stable quality in low temperature environment and highly unstable in high temperature.We also used chemistry experimental method to investigate the influence of different pH buffer.Results show that it's stabilize for TSXG in neutral and faintly acid environment,however,in alkaline environment,it's very easy to metamorphic.Research on the tissue distribution and pharmacokinetics of TSXG:In this chapter,we adopted the method of gavage by rats to investigate the tissue distribution of TSXG.Results show that we could detected drug in liver and lung,and the drug couldn't detected in heart,spleen,and kidney,indicated that it has liver and lung targeting.By the experiment of pharmacokinetics had further proven TSXG has the characteristic of long circulation.Study on pharmacodynamics of TSXG:In this chapter,we used the method of MTT by A549 and K562 cell lines to detected the anti-tumor activity in vitro,the IC₅₀of GA were 0.689?A549?and 0.021?K562??M,and the IC₅₀0 of TSXG were 12.52?A549?and 0.086?K562??M.We also adopted the S180 tumor-bearing mouse by method of gavage,and continous-dose for 7 days to detected its inhibiting effect of anti-tumor.The results show that the tumor inhibition ratio of TSXG is more higher than GA in the same dosage..