DSPE-PEG-FA-modified nanometer paclitaxel liposome and preparation method thereof

Abstract

The invention relates to a DSPE-PEG2000-FA-modified nanometer paclitaxel liposome. A molar ratio of the DSPE-PEG2000-FA to egg yolk lecithin is 0.05% to 0.15%, and a particle size of the liposome is less than 150 nm. A preparation method of the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome comprises the following steps: first, preparing a DSPE-PEG2000-FA into a DSPE-PEG2000-FA micelle; second, performing incubation on the phosphatidyl ethanolamine-polyethylene glycol2000-folic acid micelle and a paclitaxel liposome together to obtain a DSPE-PEG2000-FA-modified nanometer paclitaxel liposome. Materials, which are forbidden to be used in clinical practice, are not used as crude materials in the present invention. According to the invention, the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome has a small particle size, and the content of the DSPE-PEG2000-FA is low; besides, the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome has good drug entrapment efficiency and good colloid stability. Moreover, the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome can be absorbed effectively by an ovarian cancer cell having properties of sensitiveness to folic acid (+) and drug resistance, and the cytotoxicity of folic acid dependence is displayed; therefore, the efficacy of the DSPE-PEG2000-FA-modified nanometer paclitaxel liposome is stronger than that of a paclitaxel injection.

Description

technical field [0001] The invention relates to a medicine for treating tumors, in particular to a nano-paclitaxel liposome modified by phosphatidylethanolamine-polyethylene glycol 2000-folate and a preparation method thereof; Applications in cancer drugs. Background technique [0002] When cytotoxic drugs are used for chemotherapy of tumors, the failure of chemotherapy is often caused by the failure of the drugs to reach an effective concentration in the tumor site, and the toxicity and side effects will also increase. [0003] Ovarian cancer is the culprit of gynecological tumors, with a high mortality rate. Because more than 90% of ovarian cancers are positive for folic acid receptors with a high expression level, while normal ovarian epithelium is negative for folic acid receptors, in folic acid receptor (folic acid)-mediated targeted therapy for ovarian cancer, drugs are combined with folic acid to utilize The overexpression of folate receptors in tumor cells, with fo...

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Problems solved by technology

[0008] The one, the raw material used for preparing liposome only has stearic acid, lacks cholesterol and other substances that have a stabilizing effect on the liposome membrane, resulting in stronger fluidity of the liposome membrane, and the encapsulated medicine is easy to leak;

[0009] The second is that folic acid-coupled paclitaxel liposomes only connect folic acid and fatty acids, and there is no polyethylene glycol connection in the middle. Drug metabolism, increase in vivo circulation time and other advantages;

[0010] The third is that the particle sizes of the two liposomes made are relatively large, respectively 374.3±54.9nm and 369.3±49.3nm, so the drug efficacy is very low: IC for A549 cells (lung adenocarcinoma cells) 50 1.86±0.13μg / ml, 0.21±0.02μg / ml, respectively

[0024] Because the folic acid-paclitaxel nanoliposomes prepared by the above literature methods have low drug efficacy, which affects the clinical use effect, or uses substances that are not allowed for clinical use

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