Tumor drug-loaded microparticle preparation and preparation method thereof

A technology of microparticles and drug loading, which is applied in the direction of antineoplastic drugs, pharmaceutical formulations, drug combinations, etc., to enhance the killing effect, reduce toxic and side effects, and solve the effects of toxic and side effects

Active Publication Date: 2018-05-18
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the invention is to solve the problems existing in the prior art Drug-loaded microparticles derived from common tumor cells are impermeable Penetrate deep into the tumor to kill more tumor stem cells problem, providing a tumor drug-loaded microparticle preparation and its preparation method

Method used

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  • Tumor drug-loaded microparticle preparation and preparation method thereof
  • Tumor drug-loaded microparticle preparation and preparation method thereof
  • Tumor drug-loaded microparticle preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Tumor drug-loaded microparticle preparations produced by using chemotherapeutic drugs to induce apoptosis of mouse liver cancer stem cells

[0052] 1. Experimental materials and reagents

[0053] H22 mouse liver cancer cells, doxorubicin (with red fluorescence), carboxyfluorescein succinimidyl ester (CFSE) (green fluorescent dye).

[0054] 2. Experimental steps

[0055] 1) Cultivate H22 mouse liver cancer cells in RPMI 1640 cell culture medium, and the H22 cells are pre-diluted to 1×10 with RPMI 1640 medium 4 cells / mL to obtain a cell suspension, dilute the soft fibrin glue to a 2mg / mL solution with T7 buffer, and mix the solution with the H22 cell suspension at a volume ratio of 1:1 to obtain a mixture; Add 1 μL of thrombin (0.1U / μL) to a 96-well plate, and mix it with 50 μL of the above mixture to obtain a mixed solution. After incubating at 37°C for 15 minutes, add the mixed solution to 200 μL of RPMI 1640 for complete culture The tumor stem cell clones...

Embodiment 2

[0061] Example 2: The drug-loaded microparticles were obtained after incubating the microparticles produced by the apoptosis of mouse liver cancer stem cells induced by ultraviolet rays and chemotherapeutic drugs.

[0062] 1. Experimental materials and reagents

[0063] The H22 mouse liver cancer cells used were the same as in Example 1, the ultraviolet device was owned by a conventional cell clean bench, and the doxorubicin was the same as in Example 1.

[0064] 2. Experimental steps

[0065] 1) Culture H22 mouse liver cancer stem cells to make the cell volume reach 2×10 7 , culture method with embodiment 1.

[0066] 2) The H22 mouse liver cancer stem cells (with cell culture medium) were irradiated with ultraviolet light for 60 min.

[0067] 3) 24 hours after ultraviolet irradiation, the supernatant of the apoptotic tumor stem cell culture solution was centrifuged step by step, and the method was the same as in Example 1 to obtain microparticles of the tumor stem cell.

...

Embodiment 3

[0071] Example 3: Accumulation of drug-loaded microparticles in tumor tissue

[0072] 1. Experimental materials and reagents

[0073] The H22 mouse liver cancer cells used were the same as in Example 1, the chemotherapeutic drug doxorubicin was commercially obtained, and the BALB / C mice were purchased from the Medical Animal Center of Wuhan University.

[0074] 2. Experimental steps

[0075] 1) Culture H22 mouse liver cancer cells and liver cancer stem cells, so that the cell volume reaches 2×10 7 , wherein the culture method of H22 mouse liver cancer stem cells is the same as in Example 1, and the H22 mouse liver cancer cells are cultured with RPMI 1640 medium.

[0076] 2) Take 1×10 from the above cultured cells 7 Doxorubicin was administered to one cell to make the final concentration of doxorubicin reach 200 μg / mL, and the remaining cells continued to be cultured without any treatment.

[0077] 3) 24 hours after the administration of chemotherapeutic drugs, the drug-loa...

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Abstract

The invention provides a tumor drug-loaded microparticle preparation and a preparation method thereof. The drug-loaded microparticle preparation includes tumor stem cell apoptosis released cell vesicles and a chemotherapeutic drug wrapped in the cell vesicles as an effective component; and is prepared by mixed culture of a three-dimensional soft fibrin glue and tumor cells in a medium. The tumor drug-loaded microparticle provided by the invention is more beneficial to high enrichment in tumor tissue and deep penetration of tumors and can achieve effective uptake by common tumor cells and tumorstem cells more easily, can improve the killing power of the chemotherapeutic drug to common tumor cells and tumor stem cells, can solve the problem that common tumor cell derived drug-loaded microparticles cannot permeate to the depth parts of tumors to kill a lot of tumor stem cells, and at the same time can reduce the toxic and side effect of the chemotherapeutic drug on the body.

Description

technical field [0001] The invention relates to the technical field of drug targeting carriers, in particular to a tumor drug-loaded microparticle preparation and a preparation method thereof. Background technique [0002] Malignant tumors seriously endanger human health, and chemotherapy is one of the important means of its treatment. However, traditional chemotherapeutic drugs are mainly aimed at ordinary tumor cells, and there are a very small number of tumor stem cells (or tumor initiating cells, tumor regeneration cells) with self-renewal ability, multidirectional differentiation potential, and strong tumorigenic ability in vivo in the deep part of hypoxic tumors. Cells), which have high drug resistance due to their high expression of anti-apoptotic proteins and ABC transporters, strong DNA repair ability, etc., are the main cause of tumor recurrence and metastasis. [0003] Nano-drug delivery systems are widely used in tumor therapy due to their EPR effect, which can ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K9/16A61K47/46A61K31/704A61P35/00A61P35/02A61P35/04
CPCA61K9/1664A61K31/513A61K31/704A61K45/00A61P35/00A61P35/02A61P35/04
Inventor 甘璐杨祥良梁清乐别娜娜
Owner HUAZHONG UNIV OF SCI & TECH
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