Construction Of WGA Modified Vinblastine Cationic Liposome And Evaluation Of Its Effect On Glioma

Purpose : Gliomas are highly invasive brain tumors with increased resistance to chemotherapy and high recurrence rate.The use of chemotherapeutic drugs is limited due to the obstruction of the blood-brain barrier and severe side effects.Liposomes have been proved to be a stable and effective drug delivery system for cancer drugs.In this paper,a WGA modified vinorelbine cationic liposomes was successfully constructed and its effects on crossing the blood-brain barrier,targeting glioma cells and inhibiting tumor cell metastasis were studied.Material and method: Star-point design-response surface methodology was used to optimize the formulation of liposomes.Three factors that significantly affect the encapsulation efficiency of liposomes were selected as the study objects,and the encapsulation efficiency was selected as the evaluation index.Sephadex gel column was used to separate the encapsulated and unencapsulated liposomes to determine the encapsulation efficiency of liposomes,so the stability of liposomes was investigated.The physical and chemical properties of liposomes were investigated,including the morphology of liposomes measured by transmission electron microscopy and atomic force scanning probe microscopy.The particle size and Zeta potential of liposomes measured by Malvern laser particle size analyzer.The release rate in vitro of liposomes was investigated by two different dialysis media.Taking brain glioma cell C6 as the research object,WGA modified vinorelbine cationic liposomes were studied in vitro cell model and tumor bearing mouse model.Results: 1.The optimum formulation of vinorelbine cationic liposomes was determined by star-point design-response surface methodology.The WGA modified vinorelbine cationic liposomes were prepared according to the optimized formulation and the encapsulation efficiency was determined.The results showed that the average encapsulation efficiency of vinorelbine could reach over 90%.2.The results of physicochemical characterization of the liposomes showed that the targeted liposomes had uniform particle size and round shape,with an average particle size of about 100 nm;the encapsulation efficiency of vinorelbine was above 90%,and the release rate of vinorelbine in vitro was less than 20% within 48 hours.3.WGA modified vinorelbine cationic liposomes can significantly inhibite the survival rate of glioma cells and induced the apoptosis of glioma cells.Meanwhile,the liposomes improve the targeting of anti-cancer drugs to increase the cells uptake of drugs.4.C6 cells were used to establish the brain glioma metastasis model in vitro,and it was found that WGA modified vinorelbine cationic liposomes could significantly inhibit the formation of vasculogenic mimicry in brain glioma cells,the migration ability of tumor cells and the adhesion of brain glioma to extracellular matrix,thereby inhibiting the metastasis of tumor cells.The mechanism is related to the inhibition of the expression of tumor metastasis related proteins MMP-9,MMP-2,FAK and PI3 K.5.A mouse model of glioma was established,and it was found that the WGA modified vinorelbine cationic liposomes could effectively accumulate in the tumor tissue.The WGA modified vinorelbine cationic liposomes could significantly prolong the survival time of tumor-bearing mice and inhibit the growth of tumor volume.Furthermore,the WGA modified vinorelbine cationic liposomes had good safety during the treatment.Conclusion: In this study,a WGA modified vinorelbine cationic liposomes were constructed and characterized,and its therapeutic effect and mechanism in glioma were studied.The liposomes have good physical and chemical properties and can significantly improve the uptake of drugs in tumor cells.It can inhibit the metastasis of tumors by down-regulating the metastasis-related proteins MMP-2,MMP-9,FAK and PI3 K.In vivo,the targeting liposomes can increase the drug accumulation in the tumor tissue through EPR effect and receptor mediated effect and obtain obvious tumor therapeutic effect,which can significantly prolong the survival time of tumor-bearing mice.This study provides an effective treatment strategy for glioma,that has important scientific significance and potential clinical application value.