Preparation Of Epirubicin And Paclitaxel Co-loaded PEGylated And Targeted Liposomes,and Its Study On Antitumor Activity

Breast cancer usually occurs in malignant tumors of mammary epithelial cells.As one of the most common cancers in the world,it seriously affects the physical and mental health of patients and their families,and causes social and economic losses.At present,the main clinical use of surgical treatment,supplemented by radiotherapy,chemotherapy and other methods of treatment.However,most of the single chemotherapeutic drugs have poor targeting,toxic and side effects and short action time,which greatly restrict the effect of clinical treatment.Objective: This topic is based on the excessive expression of estrogen receptor in breast cancer cell surface,and its characteristics with its ligand specificity of estrone,prepared a loading of two kinds of chemotherapy long-acting targeted liposome preparation method was established for the determination of two kinds of chemotherapy drugs,and preparation method of long-term targeting combined with liposome were optimized for preparation were investigated in vitro characterization and anti tumor activity.Methods:(1)to establish a method for detecting the content of epirubicin,paclitaxel and epirubicin: by UV spectrophotometry,paclitaxel was determined by HPLC,the establishment of standard curve,study the intra day precision and inter day precision.(2)we optimized the preparation of epirubicin liposomes and paclitaxel liposomes respectively,including the ratio of drug to fat,the ratio of phospholipid cholesterol,the time of hydration,the time of incubation,etc.,and combined the preparation process of two liposomes,and determined the preparation method of combined liposomes.(3)according to the preparation method of determining the combined lipid body,different kinds of liposomes were prepared,including paclitaxel liposome(L-PTX),paclitaxel liposome and paclitaxel long-acting targeted liposome and paclitaxel long-acting targeted liposome,epirubicin liposome,ordinary long-acting epirubicin liposome,epirubicin liposome targeting to epirubicin,long-acting targeted liposome,combined with liposome and liposome,combined with long-acting targeted liposome,combined with long-acting targeted liposome,respectively on liposomes were characterized by different observation,including the use of dynamic light scattering particle size analyzer,particle size the distribution and Zeta potential of liposomes was observed by transmission electron microscope morphology,respectively by low speed centrifugation and dialysis method the encapsulation efficiency of paclitaxel and epirubicin were determined,and the combined lipid The stability of 4℃ and room temperature and the release in vitro under the conditions of 37℃ were investigated.(4)the cytotoxicity of single liposomes and MCF-7 cells with different doses of liposomes was investigated by MTT.Results:(1)was established for the determination of paclitaxel and epirubicin for purple Gao Xiang liquid chromatography detection method of spectrophotometry the content of two kinds of drugs in the range of determination of the concentration of a good linear relationship,the intra day and inter day precision good.(2)combined with the preparation method of two separate liposomes,and the use of CI index method for the combined use of the two drugs were explored,epirubicin,paclitaxel combined with long-acting targeted liposome preparation scheme is determined.(3)of four different formulations of paclitaxel liposome,epirubicin liposome and paclitaxel combined with epirubicin liposome were investigated,the particle size is about 120 nm,uniform,uniform particle size distribution,PDI value is about 0.1,both negatively charged liposomes.The long acting target liposomes were stable at room temperature,and the stability at 4 ℃ was better.In the in vitro release experiment,two drugs had good release behavior,and long acting fragments could prolong the release time of drugs.(5)epirubicin paclitaxel loaded long-acting targeted cytotoxic liposome on human breast cancer cell line MCF-7 wassignificantly better than the combined load of liposomes,with the prolonging of time,the toxicity increased gradually.Conclution: The preparation of epirubicin,paclitaxel liposome combined with long-term target,the preparation can better paclitaxel and epirubicin co encapsulated in liposomes,two drug combination,greatly enhanced the killing effect on cancer cells,and the use of estrone ligand on the surface of the targeted delivery of estrogen receptor overexpression the breast cancer cells,reduce the side effects of chemotherapy drugs,the introduction of the PEG long fragment,extend the two time of the drug in blood circulation,enhance the antitumor effect.In this paper,the preparation of epirubicin,paclitaxel combined with long-acting targeted liposome,high clinical value,can be combined in the hope of contemporary therapy for the treatment of cancer,the real clinical application...