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Living cell drug delivery system based on macrophages as well as preparation method and application of living cell drug delivery system

A macrophage and drug-carrying system technology, which is applied to the macrophage-based live cell drug-carrying system and its preparation field, can solve the problems of complex process, influence on drug absorption and curative effect, etc., achieve efficient treatment, and improve drug delivery efficiency Effect

Active Publication Date: 2022-05-03
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the prior art, the macrophages in the body are extracted and loaded with drugs and reinfused, and the extracted macrophages need to be subjected to steps such as in vitro expansion, drug loading, and cell sorting, and the process is complicated; using targeted modification methods, antibodies, etc. Modified on the surface of nanoparticles, intravenous or oral administration needs to overcome many physiological barriers, including mucus layer barrier, intestinal barrier, gastrointestinal emptying, blood viscosity, protein corona formation, etc., which seriously affect the absorption and efficacy of drugs

Method used

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  • Living cell drug delivery system based on macrophages as well as preparation method and application of living cell drug delivery system
  • Living cell drug delivery system based on macrophages as well as preparation method and application of living cell drug delivery system
  • Living cell drug delivery system based on macrophages as well as preparation method and application of living cell drug delivery system

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preparation example Construction

[0042] The present invention also provides a preparation method of the above macrophage-based living cell drug delivery system, comprising the following steps:

[0043] (1) Preparation of drug-loaded yeast biomimetic micromotor;

[0044] (2) The drug-loaded yeast biomimetic micromotor is introduced into an environment with macrophages, and the macrophages endocytose the drug-loaded yeast biomimetic micromotor to form a living cell drug delivery system based on macrophages.

[0045] Further, the "preparation of drug-loaded yeast biomimetic micromotor" specifically includes the following steps:

[0046] (1) Extracting the yeast cell wall from the yeast cells by an acid-base method or an enzyme digestion method;

[0047] (2) Adsorbing the drug-loaded nanoparticles into the yeast cell wall by electrostatic deposition to prepare drug-loaded yeast cell wall microcapsules;

[0048] (3) spreading the drug-loaded yeast cell wall microcapsules prepared in step (2) in a container, and ...

Embodiment

[0057] A preparation method for forming a living cell drug delivery system based on macrophages in vivo:

[0058] (1) Yeast cell wall extraction: Dissolve 500mg of Saccharomyces cerevisiae in 10mL of 1M NaOH solution, incubate at 80°C for 1h, then centrifuge at 3000rpm for 10min, discard the supernatant, wash twice with double distilled water, then add 10mL of 1M HCl , incubate at 60°C for 1 hour, then centrifuge at 3000rpm and wash twice with water, add 50mL isopropanol to wash four times, and wash twice with 50mL acetone, centrifuge to discard the supernatant, and dry to obtain empty negatively charged yeast cell walls.

[0059] (2) Preparation of curcumin-loaded cationic nanoparticles: 10 mg of curcumin and 5 mg of branched polyethyleneimine with a molecular weight of 2 kDa were dissolved in dimethyl sulfoxide, and dialyzed in water to obtain curcumin-loaded cationic nanoparticles.

[0060] (3) Preparation of drug-loaded yeast cell wall microcapsules: Dissolve 100 mg of emp...

experiment example

[0069] Add 3% dextrose sodium sulfate (DSS) into the drinking water of the mice, and drink continuously for 9 days. To prepare a mouse colitis model. From the third day, they were divided into four groups: control group (oral PBS), free curcumin group (Free Cur), curcumin nanoparticle-loaded yeast microcapsule group (CP@Y) and curcumin-loaded nanoparticle yeast biomimetic micromotor group (CP@Y-robot). The above three drugs were taken orally every two days (the equivalent of curcumin was 10 μg / g). On the 10th day, the inflammation detection probe (L-012) was injected intraperitoneally to observe the therapeutic effect of colitis using small animal imaging.

[0070] figure 1 It is a schematic diagram of the structure of a macrophage living cell drug, wherein, 1 is a macrophage, and 2 is a drug-loaded yeast biomimetic micromotor. figure 2 It is a schematic diagram of the preparation process of the drug-loaded yeast bionic micromotor. First, the yeast cell A is treated with ...

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Abstract

The invention provides a macrophage-based living cell drug-loading system, which comprises a living cell and a drug-loading yeast bionic micromotor located in the living cell, the living cell is a macrophage, the drug-loading yeast bionic micromotor comprises a yeast cell wall, and the yeast cell wall is connected with the drug-loading yeast bionic micromotor. The glucose oxidase and the catalase are semi-modified on the yeast cell wall. According to the in-vivo self-assembled living cell medicine, after entering a human body through the medicine-carrying yeast bionic micromotor, the medicine actively penetrates through the intestinal wall, enters the lymphatic system in the intestine and is endocytosed by macrophages in the lymphatic system, so that the macrophage living cell medicine is self-assembled in vivo, and the medicine can be conveyed in a targeted manner.

Description

technical field [0001] The invention belongs to the technical field of drug carriers, and in particular relates to a macrophage-based living cell drug delivery system and its preparation method and application. Background technique [0002] Macrophages are the most plastic cells in the hematopoietic system, present in all tissues and display enormous functional diversity. They play important roles in reproductive development, maintenance of homeostasis, tissue modification and immune regulation. Abnormal macrophages are closely related to many related diseases caused by inflammation, including tumors, obesity, atherosclerosis, osteoporosis, osteosclerosis, hepatitis, neurodegenerative diseases, arthritis, gastric ulcer, colitis, diabetes, etc. . It has become an important therapeutic target for inflammation-related diseases. In recent years, relying on the recruitment of macrophages in inflammatory sites, researchers have extracted and loaded macrophages in mice, and then...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K47/46A61K47/69A61K47/62A61K45/00A61P35/00A61P3/04A61P9/10A61P19/10A61P19/08A61P1/16A61P31/20A61P31/14A61P25/28A61P19/02A61P1/04A61P1/00A61P3/10
CPCA61K9/5068A61K47/6901A61K47/62A61K45/00A61P35/00A61P3/04A61P9/10A61P19/10A61P19/08A61P1/16A61P31/20A61P31/14A61P25/28A61P19/02A61P1/04A61P1/00A61P3/10Y02A50/30
Inventor 蔡林涛张保珍郑明彬潘宏唐晓帆
Owner SHENZHEN INST OF ADVANCED TECH
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