Study On Folate-mediated Targeting Tumor Cells And Paclitaxel-loaded Micelle Drug Delivery System

Tumor is the main disease that threatens people's health and life. The current clinical treatment methods of tumor such as surgery treatment, radiotherapy, chemotherapy are limited, especially for chemotherapy, and most chemotherapy drugs will cause serious side effects. As a result, it is meaningful to develop a targeting tumor cells drug delivery system. This study aims at developing a new folate-mediated targeting tumor cells micelle drug delivery system, providing the approach and theoretical basis for anti-tumor drug delivery as well as giving a nano drug-delivery system with high efficiency and low toxicity for insoluble anti-tumor drugs.This study included:prepared and characterized the drug-loading material for folate polymer micelle(FA-PEG-DSPE) and studied the hemolytic property of micelles'drug-loading material[FA-PEG-DSPE/mPEG-DSPE(n/n 1:100)]; made paclitaxel(PTX) the model drug of insoluble anti-tumor drugs, prepared the folate polymer micelle drug delivery system, characterized it by physical and chemical properties, optimized the formation and studied the freeze-drying process; Used both in-vitro and in-vivo drug efficacy evaluation methods to study the anti-tumor efficacy of PTX loaded folate polymer micelles.The concerning reactions of drug-loading material are mainly carboxyl and amino's acylation reaction triggered by DCC. HPLC method result indicated the products' purity were above 95%. The result of hemolytic property test of micelles' drug-loading material indicated that this material is not hemolytic with relatively high safety.PTX-loaded folate polymer micelles were prepared by solid-dispersing-hydration method, using the mixture of FA-PEG-DSPE/mPEG-DSPE (n/n 1:100) as the loading material. The formation was optimized by using the central composite design-response surface method basing on the single factor trials. The polymer micelles'drug-loading efficiency and entrapment percentage were determined by HPLC method. The size and distribution were determined by laser particle size analyzer and the appearance and morphology were observed by electron microscopy. And the micelles'in-vitro releasing behavior and freeze-drying method were investigated. The final optimized formulation is:the amount of PTX is 0.7mg, the volume of water is 4mL (when the loading material is 20.33mg), adding into 5% lactose before freeze-dried. The study result of micelles'physical and chemical property indicated that micelles were spherical; their size was ranging from 12 to 16nm. The result of in-vitro releasing trail indicated that PTX would be continuously released.The micelles'quality uptaken behavior result indicated that after being taken into tumor cells, drug-loading micelles distributed mainly in cytoplasm and was close to nuleus. Meanwhile, the micelles'quantity uptaken behavior result indicated that folate polymer micelle could increase tumor cells'uptaken of PTX. Both in-vitro and in-vivo drug efficacy evaluation methods were used to study the anti-tumor efficacy of PTX loaded folate polymer micelles. In-vitro drug efficacy result indicated that although different tumor cells had different sensitivity to anti-tumor drugs, polymer micelles could strengthen the anti-capacity of PTX, especially for tumor cells with high folate receptor; In-vitro drug efficacy result indicated that PTX loading folate polymer micelles could strengthen the anti-growth behavior of SGC-7901 nude tumor model, while presented little toxicity to normal tissues comparing with PTX commercial agent and normal PTX loaded polymer micelles, reflecting its obvious superiority.