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Doxorubicin long-circulating liposome targeted drug and preparation method thereof

A long-circulation liposome and doxorubicin technology, applied in the field of pharmacy, can solve the problems of short blood circulation time, poor solubility, unsatisfactory chemotherapy effect, etc., to achieve targeting and long circulation, easy to operate, cell less toxic effect

Active Publication Date: 2021-10-26
CHENGDU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the possible side effects of anticancer drugs, such as non-specific toxicity, poor solubility, short blood circulation time, etc., the chemotherapy effect is still unsatisfactory

Method used

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  • Doxorubicin long-circulating liposome targeted drug and preparation method thereof
  • Doxorubicin long-circulating liposome targeted drug and preparation method thereof
  • Doxorubicin long-circulating liposome targeted drug and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] 1. Raw material prescription

[0069] type Features Dosage Proportion Soy Lecithin Liposome material 8.3mg 37.5％ cholesterol Liposome material 2.6mg 11.8％ DSPE-PEG2000 long-circulating liposome material 2.8mg 12.7％ DSPE-PEG2000-MAL Liposome material for attachment of peptides 1.2mg 5.4％ Adriamycin active ingredient 1.2mg 5.4％ ABD peptide Bind specifically to albumin in vivo 6.0mg 27.2％

[0070] 2. Preparation process

[0071] (1) Preparation of PEGylated liposomes

[0072] Take the prescribed amount of 8.3mg soybean lecithin (S100), 2.6mg cholesterol (Chol), 2.8mg distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000), 1.2mg distearoylphosphatidylethanolamine- Polyethylene glycol 2000-maleimide (DSPE-PEG2000-MAL), the above lipid material was dissolved in 15mL of dichloromethane solvent, and the organic solvent was removed under reduced pressure at 30°C to obtain a lipid...

Embodiment 2

[0078] 1. Raw material prescription

[0079]

[0080]

[0081] 2. Preparation process

[0082] (1) Preparation of PEGylated liposomes

[0083] Take the prescription amount of 8.3mg soybean lecithin, 2.6mg cholesterol, 3.4mg DSPE-PEG2000, 0.6mg DSPE-PEG2000-MAL, dissolve the above lipid materials in 15mL of dichloromethane solvent, remove under reduced pressure at 30°C Organic solvents yield a lipid film.

[0084] (2) Preparation of drug-loaded liposomes

[0085] Hydrate the film with 123mM ammonium sulfate solution, then dialyze in a dialysis bag with a MW of 8K-14KDa for 1.5h, change the water every half an hour, then disperse the dialyzed solution with ultrasonic probe, and finally add 0.6mg of doxorubicin Incubate at 55°C for 10 minutes to obtain drug-loaded liposomes (DOX-Lip).

[0086] (3) Preparation of drug-loaded liposomes linked by ABD peptide

[0087] 2.3 mg of ABD peptide was dissolved in a small amount of HEPES buffer (pH=7.4), and stirred with the drug-...

Embodiment 3

[0089] 1. Raw material prescription

[0090] type Features Dosage Proportion Soy Lecithin Liposome material 8.3mg 45.6％ cholesterol Liposome material 2.6mg 14.3％ DSPE-PEG2000 long-circulating liposome material 3.8mg 20.9％ DSPE-PEG2000-MAL Liposome material for attachment of peptides 0.2mg 1.1％ Adriamycin active ingredient 1.8mg 9.9％ ABD peptide Bind specifically to albumin in vivo 1.5mg 8.2％

[0091] 2. Preparation process

[0092] Same as Example 1 or 2.

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Abstract

The invention discloses a doxorubicin long-circulating liposome targeted drug and a preparation method thereof, and belongs to the field of pharmaceutics. According to the doxorubicin long-circulating liposome targeted drug and the preparation method thereof, by using a long-circulating liposome material and introducing ABD peptide capable of being specifically combined with endogenous albumin into liposome by using a reactive group on the liposome, the combination of a drug with albumin after entering the body is realized, adsorption with other proteins in the body is reduced, so that the circulating time of the drug in blood is prolonged, meanwhile, the lipidosome adsorbing the albumin is combined with an albumin receptor on the surface of a tumor cell, so that the targeting property of the drug on a tumor cell is improved.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a long-circulation liposome targeting drug of doxorubicin and a preparation method thereof. Background technique [0002] Cancer has always been the leading cause of death in the world. According to the global new cancer statistics in 2020, breast cancer replaced lung cancer and became the largest cancer in the world, which is seriously endangering human life. Clinical chemotherapy remains the main treatment modality for cancer. However, due to the possible side effects of anticancer drugs, such as non-specific toxicity, poor solubility, and short blood circulation time, the effect of chemotherapy is still not ideal. Therefore, drug sustained and controlled release nanotechnology has become a research hotspot, which is used to deliver the desired drug to the tumor site to achieve the goal of reducing toxic side effects and improving therapeutic effect. [0003] Due to their ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/704A61K47/24A61K47/28A61K47/62A61P35/00
CPCA61K31/704A61K47/62A61K47/6911A61K47/24A61K47/28A61P35/00Y02A50/30
Inventor 李寒梅尹丹邹亮唐川鄂王瑶
Owner CHENGDU UNIV
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