Cross-linked mitochondrial targeting doxorubicin liposome and preparation method thereof

Abstract

The invention relates to a cross-linked mitochondrial targeting doxorubicin liposome. The cross-linked mitochondrial targeting doxorubicin liposome is composed of doxorubicin hydrochloride, phospholipid, cholesterol and a cross-linkable mitochondrial targeting pegylated phospholipid medicinal material, a mass ratio of doxorubicin hydrochloride to the phospholipid is 1:(5-20), a molar ratio of the phospholipid to cholesterol to the cross-linkable mitochondrial targeting pegylated phospholipid medicinal material is (50-90):(2-47):(3-8), the structural formula of the cross-linkable mitochondrial targeting pegylated phospholipid medicinal material is shown in the specification, and n in the structural formula is 10, 12, 14 or 16. The invention also provides a preparation method of the liposome. The cross-linked mitochondrial targeting doxorubicin liposome has the advantages of mitochondrial targeting, large absorbed quantity of tumor cells, and high safety.

Description

technical field [0001] The invention belongs to the technical field of medicine and its preparation, and in particular relates to an antitumor drug liposome and a preparation method thereof. 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. Doxorubicin is a commonly used drug in cancer chemotherapy, but the extensive use of chemotherapy drugs such as doxorubicin can easily lead to drug resistance in cells. 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...

AI Technical Summary

Problems solved by technology

The micellar drug-loading system has the function of targeting mitochondria, but there are the following problems in the process of delivering the drug doxorubicin to the mitochondria of tumor cells: (1) folic acid is a hydrophobic molecule, in an aqueous environment, according to the hydrophilic and hydrophobic properties, Folic acid molecules tend to be distributed in the hydrophobic core of micelles rather than in the hydrophilic outer layer of micelles, resulting in a low uptake rate of folic acid-modified carriers by cells and affecting the antitumor effect; (2) triphenylphosphine is An organophosphorus pesticide that is irritating to the eyes, upper respiratory tract, mucous membranes, and skin, and is neurotoxic

Therefore, the use of triphenylphosphine in medicinal materials has potential safety hazards

There is no report about doxorubicin liposomes with mitochondrial targeting function

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