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Liposome co-loaded with alkannin and anthracycline chemotherapeutic drugs as well as preparation method and application of liposome

An anthracycline, shikonin technology, applied in the application of anti-tumor immunotherapy, in the field of liposome preparation, can solve problems such as low bioavailability, poor water solubility, toxic and side effects, and achieve high drug encapsulation efficiency , the effect of reducing leakage, reducing the use of

Active Publication Date: 2021-07-30
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, while inducing effective ICD effects, it can also produce severe toxic side effects
[0004] The traditional Chinese medicine shikonin is also an effective ICD inducer. It has the characteristics of an ICD inducer. However, due to its poor water solubility, low bioavailability, and high toxicity, it has not been used as an anticancer drug in clinical practice.
There is no report on the preparation of ICD inducer anthracycline chemotherapeutics and shikonin into a co-loaded complex for anti-tumor

Method used

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  • Liposome co-loaded with alkannin and anthracycline chemotherapeutic drugs as well as preparation method and application of liposome
  • Liposome co-loaded with alkannin and anthracycline chemotherapeutic drugs as well as preparation method and application of liposome
  • Liposome co-loaded with alkannin and anthracycline chemotherapeutic drugs as well as preparation method and application of liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] A preparation method comprising shikonin and mitoxantrone hydrochloride co-loaded liposomes, which mainly includes the following steps:

[0044] (1) Dissolve hydrogenated soybean lecithin (HSPC), cholesterol (Chol), and PEGylated phospholipid (DSPE-mPEG2000) (mass ratio 95.5:5.2:0.5) in chloroform, evaporate the organic solvent under reduced pressure, and form a dry lipid membrane;

[0045] (2) Add 200mM copper gluconate solution (adjust the pH to 7.4 with triethanolamine), hydrate at 55-65°C for 30 minutes, and pass through a polycarbonate filter membrane to form a liposome membrane with copper gluconate inside and outside The nano-sized liposome of the solution, utilizes the agarose gel chromatographic column to exchange the liposome external water phase to be HEPES buffer salt;

[0046] (3) Add shikonin DMSO solution to the liposome prepared in step (2), incubate at 55-65° C. for 30 min, then add mitoxantrone hydrochloride aqueous solution, continue to incubate for ...

Embodiment 2

[0049] Screening the Synergistic Ratio of Mitoxantrone Hydrochloride and Shikonin in Co-loaded Preparations

[0050] 1. Screen synergy ratio by cytotoxicity test

[0051] Cells B16F10 (melanoma cells) in the logarithmic growth phase were spread in a 96-well plate with 3000 cells per well, adhered to the wall for 12 hours, and different molar ratios were prepared according to the method in Example 1 (mitoxantrone: shikonin=10 :1,5:1,2:1,1:1,1:2,1:5,1:10,1:20) shikonin and mitoxantrone were co-loaded liposomes with different molar ratios (Mitoxantrone:Shikonin=10:1,5:1,2:1,1:1,1:2,1:5,1:10,1:20) liposome, shikonin and mitoxantrone hydrochloride aqueous physical mixture, were diluted with culture medium to the required concentration (co-loaded liposome concentration gradient: 10 μg / ml, 5 μg / ml, 2.5 μg / ml, 1.25 μg / ml, 0.625 μg / ml , 0.312μg / ml, 0.156μg / ml, 0.078μg / ml, 0.039μg / ml; physical mixture concentration gradient: 2.5μg / ml, 1.25μg / ml, 0.625μg / ml, 0.312μg / ml, 0.156μg / ml , 0...

Embodiment 3

[0059] Screening of the ratio of ICD effect induced by mitoxantrone hydrochloride and shikonin co-loaded liposomes synergistically

[0060] Cells B16F10 (melanoma cells) in the logarithmic growth phase were spread in a 24-well plate with 100,000 cells per well, adhered to the wall for 12 hours, and different molar ratios were prepared according to the method in Example 1 (mitoxantrone: shikonin=10 :1,1:1,1:10) of shikonin and mitoxantrone co-loaded liposomes, preparation of shikonin single-loaded liposomes, preparation of mitoxantrone single-loaded liposomes, using medium Dilute the single-loaded and co-loaded liposome solutions until the liposomes contain a total drug amount of 5 μg / ml, incubate in the incubator for 24 hours, and use the ATP kit to measure the ATP concentration released by the cells in the medium. Experimental results such as image 3 .

[0061] The results showed that different molar ratios of shikonin and mitoxantrone co-loaded liposomes could synergistic...

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Abstract

The invention discloses a preparation method of lipidosome containing alkannin and anthracycline chemotherapeutic drugs and an application of the lipidosome in synergistic anti-tumor immunotherapy, and belongs to the technical field of pharmaceutical preparations. Firstly, alkannin and an anthracycline drug mitoxantrone or adriamycin are simultaneously encapsulated in a liposome, a synergistic proportion is screened by using a co-loaded liposome through a cytotoxicity experiment, an uptake experiment and ICD induction capability, and the prepared dual-drug-loading liposome has a pH / GSH dual-response release characteristic, can deliver a drug to a tumor tissue, the anti-tumor effects is synergistically induced, the administration dosage of the two drugs is reduced, the toxic and side effects of the drugs are reduced, and the purposes of enhancing the effect and reducing the toxicity are achieved.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to the preparation of a liposome containing shikonin and anthracycline chemotherapeutics and its application in anti-tumor immunotherapy. Background technique [0002] Immunotherapy refers to the treatment methods that artificially enhance or suppress the immune function of the body to achieve the purpose of treating diseases, including tumor vaccines, immune checkpoint inhibitors, etc. Recently, immunotherapy has shown good advantages in the treatment of cancer and has received more and more attention. Due to the low response rate of single immunotherapy, immunotherapy is often used in combination with chemotherapy drugs to enhance its effect. Some chemotherapeutic drugs such as doxorubicin, mitoxantrone, cyclophosphamide, oxaliplatin and other chemotherapeutic drugs themselves can also induce apoptosis tumors to produce related antigens, thereby ac...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/122A61K45/06A61K31/136A61P35/00
CPCA61K9/127A61K31/122A61K45/06A61K31/136A61K47/28A61P35/00A61K2300/00
Inventor 刘洪卓李金菠何仲贵周双王永军
Owner SHENYANG PHARMA UNIVERSITY
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