Cross-linked mitochondrial targeting doxorubicin liposome and preparation method thereof

A technology of doxorubicin lipid and mitochondria, which is applied in the field of anti-tumor drug liposome and its preparation, can solve the problems of affecting anti-tumor effect, low carrier uptake rate, neurotoxicity, etc., and achieve good tumor tissue targeting, Avoid early release, long cycle effects

Active Publication Date: 2015-11-18
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

Method used

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  • Cross-linked mitochondrial targeting doxorubicin liposome and preparation method thereof
  • Cross-linked mitochondrial targeting doxorubicin liposome and preparation method thereof
  • Cross-linked mitochondrial targeting doxorubicin liposome and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0038] Example 1

[0039] The adriamycin liposomes described in this embodiment are composed of adriamycin, soybean lecithin, cholesterol, and cross-linkable mitochondrial targeting pegylated distearoylphosphatidylethanolamine (DSPE-PEG2000-KLA). The mass ratio of doxorubicin hydrochloride to soybean lecithin is 1:5. The molar ratio of soybean lecithin, cholesterol and DSPE-PEG2000-KLA is 50:47:3, and the structural formula of DSPE-PEG2000-KLA is

[0040]

[0041] The preparation method is as follows:

[0042] (1) Preparation of DSPE-PEG2000-KLA

[0043] Distearoylphosphatidylethanolamine-polyethylene glycol 2000-maleimide (DSPE-PEG2000-Mal), polypeptide D-(KLAKLAK) 2 -C 5 And triethylamine as raw materials, peptide D-(KLAKLAK) 2 -C 5 The molar ratio of, triethylamine and DSPE-PEG2000-Mal is 1:1:1;

[0044] Under the protection of nitrogen, mix DSPE-PEG2000-Mal, triethylamine and chloroform uniformly to obtain the first solution. The amount of chloroform is such that the concentration...

Example Embodiment

[0049] Example 2

[0050] The adriamycin liposome in this embodiment is composed of adriamycin, egg yolk lecithin, cholesterol, and mitochondrial targeting pegylated dimyristoylphosphatidylethanolamine (DMPE-PEG2000-KLA). The mass ratio of doxorubicin hydrochloride to egg yolk lecithin is 1:20. The molar ratio of egg yolk lecithin, cholesterol and DMPE-PEG2000-KLA is 90:2:8, and the structural formula of DMPE-PEG2000-KLA is

[0051]

[0052] The preparation method of the liposome is as follows:

[0053] (1) Preparation of DMPE-PEG2000-KLA

[0054] Based on dimyristoylphosphatidylethanolamine-polyethylene glycol 2000-maleimide (DMPE-PEG2000-Mal), polypeptide D-(KLAKLAK) 2 -C 5 And 4-dimethylaminopyridine as raw material, peptide D-(KLAKLAK) 2 -C 5 The molar ratio of 4-dimethylaminopyridine and DMPE-PEG2000-Mal is 2:2:1;

[0055] Under the protection of nitrogen, mix DMPE-PEG2000-Mal, 4-dimethylaminopyridine, and dichloromethane to obtain the first solution. The amount of dichloromethan...

Example Embodiment

[0060] Example 3

[0061] The adriamycin liposomes described in this embodiment are composed of adriamycin, hydrogenated lecithin, cholesterol and mitochondrial targeting pegylated dipalmitoylphosphatidylethanolamine (DPPE-PEG2000-KLA). The mass ratio of doxorubicin hydrochloride to hydrogenated lecithin is 1:10. The molar ratio of hydrogenated lecithin, cholesterol and DPPE-PEG2000-KLA is 70:25:5, and the structural formula of DPPE-PEG2000-KLA is

[0062]

[0063] (1) Preparation of DPPE-PEG2000-KLA

[0064] Take dipalmitoylphosphatidylethanolamine-polyethylene glycol 2000-maleimide (DPPE-PEG2000-Mal), polypeptide D-(KLAKLAK) 2 -C 5 And N,N-diisopropylethylamine as raw materials, peptide D-(KLAKLAK) 2 -C 5 The molar ratio of N,N-diisopropylethylamine and DPPE-PEG2000-Mal is 3:3:1;

[0065] Under the protection of nitrogen, mix DPPE-PEG2000-Mal, N,N-diisopropylethylamine, and methylene chloride uniformly to obtain the first solution. The amount of methylene chloride is such that the ...

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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...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/34A61K31/704A61P35/00
Inventor 李莉顾忠伟姜雷孙家维
Owner SICHUAN UNIV
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