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CD44-mediated intelligent response type polymer micelle as well as preparation and application thereof

A polymer gel and polymer technology, applied in the field of micelles, can solve the problems of release and diffusion, uncontrolled drug release, unsatisfactory, etc., and achieve the effect of simple synthesis process and increased cell uptake

Inactive Publication Date: 2021-04-13
SUZHOU POLYTECHNIC INST OF AGRI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] (1) Low efficiency of tumor targeting and endocytosis
On the one hand, the EPR effect only realizes the accumulation of nanomicelles in the tumor site, and the subsequent process of cell entry is affected by the hydrophilic shell of micelles, which is often unsatisfactory, which leads to low drug concentration in tumor cells.
[0006] (2) Uncontrolled drug release
After entering the cell, the drug cannot be rapidly released from the nanomicelle and diffuse to its target site, such as the nucleus
These problems lead to too low intracellular drug concentration to achieve the expected antitumor effect

Method used

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  • CD44-mediated intelligent response type polymer micelle as well as preparation and application thereof
  • CD44-mediated intelligent response type polymer micelle as well as preparation and application thereof
  • CD44-mediated intelligent response type polymer micelle as well as preparation and application thereof

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Experimental program
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Effect test

Embodiment 1

[0046] 1. Synthesis of HA-DA

[0047] Weighed 388 mg (0.5 mmol) of HA and dissolved it in 30 mL of deionized water, and added EDC·HCl (192 mg, 1 mmol) and NHS (115 mg, 1 mmol) at 45°C to activate the carboxyl groups of HA for 1 h. Weigh 92mg (0.5mmol) of DA and dissolve it in 20mL of absolute ethanol, slowly drop it into the HA solution, and react at 45°C for 24h. The product was dialyzed in distilled water for 3-4 hours to remove by-products, and lyophilized to obtain HA-DA.

[0048] 2. Synthesis of His-HA-DA

[0049] Weigh 194 mg (0.5 mmol) of HA-DA and dissolve it in 10 mL of deionized water, add EDC·HCl (96 mg, 0.5 mmol) and NHS (57.5 mg, 0.5 mmol) at 45 ° C to activate the carboxyl group for 30 min, then add His (155 mg, 1mmol), reacted at room temperature for 12h. The product was dialyzed 5-6 times in distilled water and freeze-dried to obtain His-HA-HD.

[0050] The synthetic route of His-HA-HD is as follows:

[0051]

[0052] 3. Preparation of drug-loaded micelle...

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Abstract

The invention relates to a CD44-mediated intelligent response type polymer micelle as well as preparation and application thereof. The invention discloses a pH responsive polymer micelle. The pH responsive polymer micelle comprises a micelle body formed by a polymer; the polymer comprises hyaluronic acid; and the hyaluronic acid is connected with alkylamine and histidine through chemical bonds. The pH responsive polymer micelle can be used for preparing an antitumor drug carrier. The invention provides a CD44 targeting micelle based on polymer histidine-hyaluronic acid-alkylamine. The CD44 targeting micelle is used for delivering an antitumor drug; and due to the pH sensitivity of the micelle, the antitumor drug can be released from the polymer micelle.

Description

technical field [0001] The invention relates to the field of micelles, in particular to a CD44-mediated smart responsive polymer micelles and its preparation and application. Background technique [0002] According to statistics, cancer has become one of the main causes of human death. At present, drug therapy has become an important means of clinical treatment of tumors. Today's common tumor treatment method is still based on chemotherapy, which has different degrees of adverse effects on the patient's physical condition, and is prone to vomiting, hair loss and other adverse reactions, and is prone to drug resistance; and because chemotherapy drugs lack tumor target tropism, and is also toxic to normal cells during use. Albumin nanoparticles that are currently on the market are expensive to manufacture, have unsatisfactory tumor targeting, and cannot quickly and effectively release the loaded drugs or genes. [0003] Micellar delivery system is one of the most promising ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/36A61K31/704A61P35/00
CPCA61K9/1075A61K47/36A61K31/704A61P35/00
Inventor 杨舒迪陈维良宋京城高岳
Owner SUZHOU POLYTECHNIC INST OF AGRI
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