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Preparation method and application of erythrocyte membrane-coated acid-sensitive polymer prodrug nano drug delivery system

A nano-drug delivery system and erythrocyte membrane technology, applied in the fields of polymer chemistry and nano-formulation, can solve the problems of phagocytosis of reticuloendothelial cells, increase the difficulty of nano-particle preparation, etc., and achieve good drug release characteristics, reduced toxicity, and cycle time. long effect

Inactive Publication Date: 2016-04-20
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, studies have found that the body will produce an anti-PEG immune response to PEGylated nanocarriers, thereby stimulating their phagocytosis by reticuloendothelial cells
Due to the good circulation characteristics of red blood cells in the body, some researchers modified the surface of nanoparticles to simulate red blood cell membranes based on the structural characteristics of red blood cell membranes to achieve the purpose of prolonging the circulation time in vivo, but this method requires the identification and purification of red blood cell membrane proteins Work with chemical connections undoubtedly increases the difficulty of preparing nanoparticles, and it is difficult to make nanocarriers completely simulate the structural characteristics of red blood cell membranes.

Method used

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  • Preparation method and application of erythrocyte membrane-coated acid-sensitive polymer prodrug nano drug delivery system
  • Preparation method and application of erythrocyte membrane-coated acid-sensitive polymer prodrug nano drug delivery system
  • Preparation method and application of erythrocyte membrane-coated acid-sensitive polymer prodrug nano drug delivery system

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Embodiment 1

[0038] (1) Preparation of erythrocyte membrane vesicles

[0039] 1) Take a mouse weighing about 20g, and inject 0.2ml of 2% pentobarbital sodium solution into the intraperitoneal cavity. After complete anesthesia, cut open the xiphoid process and above, expose the heart, insert a needle from the left ventricle, and take heparin Take blood (approximately 1ml) from a sodium-rinsed syringe, and transfer it to EP tubes containing 2ml heparin sodium;

[0040] 2) Put the whole blood in a centrifuge and centrifuge at 900g for 20min. Discard the supernatant and leave a dark red precipitate. Take 3 times the volume of the precipitate and put it in 1*PBS, blow it evenly, and put it in the centrifuge for centrifugation. 2500g, 15min. This is the first washing, repeat the operation three times;

[0041] 3) After the last operation above, discard the supernatant and leave the precipitate, take 1*PBS equivalent to the precipitate and blow it into a centrifuge tube, take 950ul of 0.2mM EDTA...

Embodiment 2

[0049] Configure macromolecule-loaded paclitaxel prodrug (PGSC-PTX) and red blood cell-wrapped polymer-loaded paclitaxel prodrug (RBCm / PGSC-PTX) 1mg / ml, let it stand for 2 minutes after ultrasonication for 5 minutes, and measure its concentration with a Malvern laser particle size analyzer. particle size and particle size distribution, figure 2 (A, B) show the size distribution of nanoparticles. The average particle sizes of PGSC-PTX and RBCm / PGSC-PTX are about 50nm and 100nm, respectively.

Embodiment 3

[0051] The morphology of PGSC-PTX and RBCm / PGSC-PTX was observed by transmission electron microscope (TEM), and the samples were prepared by negative staining with 1% phosphotungstic acid, as follows: (1) put a drop of sample solution on the copper grid, (2) ) Dry in the air for about 10 minutes, absorb excess liquid with filter paper, (3) drop a drop of 1% phosphotungstic acid on the copper grid, dry at room temperature for 5 minutes, absorb excess dye solution with filter paper, (4) wait The samples were observed under a transmission electron microscope after drying. figure 2 (C, D) are transmission electron microscope pictures of two kinds of nanoparticles, PGSC-PTX and RBCm / PGSC-PTX. The shapes of the two kinds of nanoparticles are relatively regular and spherical.

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Abstract

The invention discloses a preparation method and an application of an erythrocyte membrane-coated acid-sensitive polymer prodrug nano drug delivery system, wherein the polymer is formed by connecting sodium polyglutamate and carbocisteine through a peptide bond and then is bonded with an anti-cancer drug taxol to form the polymer prodrug; and the polymer prodrug is coated by an erythrocyte membrane to obtain an erythrocyte membrane-coated acid-sensitive polymer drug delivery system. The drug delivery system has the following characteristics that the particle size is about 100nm, and the shape is a sphere; the drug delivery system is relatively stable in a phosphate buffer and serum; the drug release character is relatively good in an acid environment; the toxicity is obviously reduced in cell experiments; the ingestion of the system by macrophage is obviously reduced; without destructive effect on erythrocyte, the system can be applied to intravenous injection; the circulating time of the system in blood is remarkably longer than that of polymer; and the system has an obvious inhibiting effect on the tumor growth of lung cancer.

Description

technical field [0001] The invention relates to the technical field of polymer chemistry and nano-preparation, in particular to the preparation and application of a long-cycle acid-sensitive polymer drug delivery system for antitumor drug delivery. Background technique [0002] Chemotherapy is one of the most common treatments for malignant tumors, but statistics show that chemotherapy has not led to a substantial reduction in the mortality of cancer patients in clinical practice. Paclitaxel is one of the most effective chemotherapy drugs, mainly used in the treatment of lung cancer, ovarian cancer and breast cancer. Paclitaxel has the function of polymerizing and stabilizing intracellular microtubules, causing fast-dividing tumor cells to be firmly fixed in the mitotic stage, so that the microtubules are no longer separated, and can block cells in the G2 and M phases of the cell cycle, allowing cancer cells to replicate Died by being blocked. The low water solubility of p...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K31/337A61P35/00
CPCA61K31/337
Inventor 王依婷南丽娟彭婷孙磊周靖娥肖晔王华高猎防闫志强王镜朱建中俞磊
Owner EAST CHINA NORMAL UNIV
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