Cross-linkable mitochondria-targeted PEGylated phospholipid medicinal material and its preparation method and application

Abstract

The cross-linkable mitochondria-targeting pegylated phospholipid pharmaceutical material of the present invention has the following structural formula: n=10, 12, 14, 16. Preparation method: using fatty acid acylphosphatidylethanolamine-polyethylene glycol-maleimide, polypeptide D-(KLAKLAK)2-C5 and organic base as raw materials, polypeptide, organic base, fatty acid acylphosphatidylethanolamine-polyethylene glycol The mol ratio of alcohol-maleimide is (1~3):(1~3):1; under nitrogen protection, fatty acid acylphosphatidylethanolamine-polyethylene glycol-maleimide, organic base Mixing with the first solvent to obtain a first solution, dissolving the polypeptide in a second solvent to obtain a second solution, mixing the first solution and the second solution, and stirring and reacting for 12 to 48 hours at 20 to 40° C. in the dark. The drug-loaded liposome prepared by using the medicinal material can further improve the tumor treatment effect, reduce toxic and side effects and facilitate long-term storage.

Description

technical field [0001] The invention belongs to the technical field of medicine and its preparation, and in particular relates to a phospholipid medicinal material and its preparation method and application. Background technique [0002] Chemotherapy is one of the main ways to treat cancer, but the mortality rate of cancer patients after chemotherapy is still high. Multidrug resistance (MDR) is one of the main reasons for clinical chemotherapy failure. The drug resistance of tumor cells can be divided into two categories: congenital and acquired. Studies have shown that changes in tumor cell genes or gene phenotypes lead to changes in apoptosis pathways, which eventually lead to the emergence of tumor innate drug resistance. Mitochondria are the "power factory" of the cell and also the "suicide arsenal", which can initiate the apoptosis pathway. Therefore, the innate drug resistance of tumor cells is closely related to the abnormal function of mitochondria. Taking mitocho...

AI Technical Summary

Problems solved by technology

However, DKD still has the following deficiencies: 1) DKD does not have a long-term circulation function, resulting in the rapid clearance of DKD liposomes in blood vessels, which is not conducive to the delivery of anticancer drugs across the vascular barrier; 2) the drug-loaded liposomes prepared by DKD Nano-liposomes are nano-aggregates formed by the assembly of molecules through non-covalent bonds. They are unstable in the blood circulation and transmembrane process, and are easy to disintegrate, resulting in the early release of drugs before reaching the target and failing to achieve therapeutic effects. And after the medicine goes off the target and enters the normal tissue, it is very easy to cause serious toxic and side effects; 3) because the molecular structure of DKD does not have a hydrophilic protective layer, the prepared DKD liposomes are prone to agglomeration after being placed for a period of time, and the particle size becomes larger. It is not conducive to the entry of liposomes from blood vessels into tissues, thereby reducing the targeting of tumor tissues, and there are safety hazards such as blocking capillaries

Therefore, the long-term stability of DKD liposomes is not good, which is not conducive to long-term storage

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