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Drug-loading nano-liposome, and preparation method and application thereof

A nano-liposome and drug-carrying nanotechnology, which is applied in the application field of tumor treatment, can solve the problems of ceramide being difficult to mix with phospholipid molecules and poor treatment effect.

Inactive Publication Date: 2015-09-23
TAIZHOU MABTECH PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In order to solve the above-mentioned deficiencies in the prior art, the present invention constructs a nanoliposome (Lipo-ADR-Cer) that co-loads PEG-C16-ceramide and doxorubicin, which fully solves the problem of separate administration of ceramide and chemotherapeutic drugs. The problem of poor therapeutic effect, and the problem that ceramide in nanoliposomes of ceramide is not easy to mix with phospholipid molecules

Method used

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  • Drug-loading nano-liposome, and preparation method and application thereof
  • Drug-loading nano-liposome, and preparation method and application thereof
  • Drug-loading nano-liposome, and preparation method and application thereof

Examples

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Effect test

Embodiment 1

[0053] Implementation Example 1: Preparation of Lipo-ADR-Cer liposomes of the present invention and Lipo-ADR liposome blank liposomes

[0054] The composition and proportion of the blank liposome of PEG-Ceramide modified doxorubicin liposome: A hydrogenated soybean lecithin 24 mg (30.57nmol, 56.35%mol); B cholesterol 8mg (20.69nmol, 38.14%mol); C PEG2000-DSPE 2 mg (0.71 nmol, 1.31% mol); D PEG2000-C16-Ceramide 6 mg (2.28 nmol, 4.20%). PEG2000-DSPE and PEG2000-C16-Ceramide were purchased from Avanti Polar Lipids Company in the United States, cholesterol was purchased from Sigma Company, and hydrogenated soybean lecithin was purchased from Lipoid Company. The composition and ratio of the control doxorubicin liposome blank liposome: A hydrogenated soybean lecithin 24 mg (30.57nmol, 56.50%mol) B cholesterol 8mg (20.69nmol, 38.24%mol) C PEG2000-DSPE 8mg (2.85nmol ,5.27%mol). According to the above composition, accurately weigh the above ingredients into a 1.5 ml EP tube.

[00...

Embodiment 2

[0056] Implementation Example 2: Preparation of Lipo-ADR-Cer liposomes and Lipo-ADR liposome drug-loaded liposomes of the present invention

[0057]Take the liposome solution after dialysis in Example 1, add a pre-prepared 10 mg / ml doxorubicin solution (dissolved in MilliQ water, doxorubicin purchased from Dalian Meilun Biological Co., Ltd.), add 1ml blank liposome 75ul doxorubicin stock solution, the mixed solution during the drug loading process was placed in a water bath at 65°C for 15-20 min.

[0058] For removing the free doxorubicin of small molecules, the method of adopting dialysis is as follows: the prepared doxorubicin liposome solution is put into the dialysis bag that the molecular weight cut off is 1000KDa, and the dialysate is the HEPES solution (pH 7.4 of 1 L). ), the dialysis time is 6-8 hours, the fluid is changed twice, and the dialysis should be protected from light. Lipo-ADR-Cer liposomes and Lipo-ADR liposomes were obtained after dialysis, and were stor...

Embodiment 3

[0059] Implementation example 3: formulation optimization of co-loaded liposome Ceramide and ADR liposome

[0060] (1) The composition and ratio of C16-Ceramide co-loaded doxorubicin liposome blank liposomes: A Hydrogenated soybean lecithin 24 mg (30.57nmol, 56.35%mol) B Cholesterol 8mg (20.69nmol, 38.14%mol) C PEG2000-DSPE 2mg (0.71nmol, 1.31%mol) D C16-Ceramide 1.23mg (2.28nmol, 4.20%). PEG2000—DSPE and C16-Ceramide were purchased from Avanti Polar Lipids Company in the United States, cholesterol was purchased from Sigma Company, and hydrogenated soybean lecithin was purchased from Lipoid Company. The preparation process of liposomes co-loading C16-Ceramide and doxorubicin is as in Example 2.

[0061] (2) The composition and proportion of the blank liposomes co-loaded with doxorubicin liposomes by C6-Ceramide: hydrogenated soybean lecithin 24 mg (30.57 nmol, 56.35% mol) B cholesterol 8 mg (20.69 nmol, 38.14% mol) C PEG2000-DSPE 2mg (0.71nmol, 1.31%mol) D C6-Ceramide 0.91...

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Abstract

The invention discloses a drug-loading nano-liposome, and a preparation method and application thereof. The invention relates to the field of synthesis and treatment of nano-liposomes, in particular to a nano-liposome co-loading PEG-C16-ceramide and adriamycin, the preparation method of the nano-liposome, and the application of the nano-liposome to the field of tumor treatment. The nano-liposome (Lipo-ADR-Cer) co-loading the PEG-C16-ceramide and the adriamycin is constructed, the preparation method and the stability of the Lipo-ADR-Cer are disclosed, and the basic representation, the in-vitro release process and the in-vitro cell transfection endocytosis efficiency of the liposome are not changed. In terms of tumor drug-resistant cell strains, the in-vitro cytotoxicity, the in-vitro apoptosis-promoting ability and the in-vivo treatment effect of the Lipo-ADR-Cer are improved. The PEG-C16-ceramide and the adriamycin can be co-loaded, the adriamycin IC50 of the drug-resistant cells can be reduced, and the nano-liposome can be used for treating drug-resistant tumor cells.

Description

technical field [0001] The invention relates to the field of medical technology, more specifically, the invention discloses a nano-liposome co-loaded with PEG-C16-ceramide and doxorubicin, a preparation method thereof, and an application in the field of tumor treatment. Background technique [0002] Multidrug resistance (MDR) refers to the drug resistance phenomenon that is induced by one chemotherapy drug and is resistant to other anticancer drugs with different mechanisms of action. important cause of relapse. The formation mechanism of multidrug resistance is complex, with many influencing factors, involving multiple aspects from cell membrane, cytoplasm to nucleus, and these influencing factors may jointly play a role in the formation of multidrug resistance. According to literature reports, the decline of ceramide content in tumor cells is an important mechanism of tumor cell drug resistance (J. Liu. Foroozesh. A review of ceramide analogs as potential anticancer ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/704A61K47/34A61P35/00
Inventor 钱卫珠
Owner TAIZHOU MABTECH PHARM CO LTD
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