Preparation And Evaluation Of PH-sensitive Nano Drug Delivery System Based On Polysaccharide Carrier

Cancer is increasingly becoming a major threat to human health,and the benefits of treatment have been severely weakened by the obvious side effects of traditional anti-tumor drugs and the resistance of the tumor itself.It is of great significance to use natural polymer materials as carrier to enhance the enrichment of anti-tumor drugs in the lesion site and realize the intelligent release of drugs,which can reduce the toxic and side effects of drugs and improve the therapeutic benefits.This topic designed and synthesized with carboxymethyl chitosan(CMCS)and hyaluronic acid(HA)as the carrier of nano drug delivery system,the use of acid sensitive linker coupling polymer carrier and antitumor drugs,and formed by self-assembly nanometer particles,the systemic stability of the system and the diseased cells of passive targeting are enhanced,and the acid sensitive linker can break up in tumor cells in the acidic environment made the intelligent drug release to kill tumor cells.The main contents of the study are as follows:(1)Carboxymethyl chitosan was conjugated with adriamycin by imine bond and self-assembled in aqueous solution to form polymer precursor nanoparticles,which improved the water solubility of adriamycin and the passive targeting of the system.The effect of molecular weight of carboxymethyl chitosan on drug loading was investigated.The morphology and particle size distribution of nanoparticles,in vitro simulated release characteristics and in vitro cytotoxicity were measured.Through cell uptake studies,it was found that polymer prodrug nanoparticles could effectively enter tumor cells and accumulate in the nucleus.(2)The p H-sensitive nano drug delivery system was prepared with hyaluronic acid as the polymer carrier.The solubility and active targeting of adriamycin were improved by the high water solubility of hyaluronic acid and high affinity to CD44 receptor.The p H-sensitive release characteristics of the nano-drug delivery system were studied,and the results showed that the imine bond breaking could release adriamycin rapidly and effectively kill tumor cells in a low p H.(3)The HA-hyd-DNR/CUR nano drug delivery system was prepared by coupling daunorubicin(DNR)and curcumin(CUR)to hyaluronic acid by hydrazone bond(hyd).The morphology and particle size of nanoparticles were studied and the stability and in vitro release characteristics of the nano drug delivery system were investigated.The growth inhibition effect of curcumin,daunorubicin,curcumin/daunorubicin and nano drug delivery system against the esophageal cancer cell line Kyse was compared.(4)The HA-hyd-DNR/RES acid sensitive nano drug delivery system was prepared by coupling hydrazone bond and ester bond,which improved the solubility of daunorubicin and resveratrol(RES).HA-hyd-DNR/RES polymer drug chelates are amphiphilic and can be self-assembled in aqueous solution to obtain prodrug nanoparticles.TEM and DLS were used to study the morphology and particle size of nanoparticles.The stability and in vitro release characteristics of nano-drug delivery system were investigated,and the growth inhibition of resveratrol,daunorubicin,resveratrol + daunorubicin and nano-drug delivery system on human cervical cancer cell line Hela and the cellular endocytosis of nanoparticles were compared.