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Injectable drug-loaded temperature-sensitive hydrogel capable of enhancing anti-tumor immunity and preparation and application thereof

An anti-tumor immune, temperature-sensitive hydrogel technology, applied in the field of medicine, can solve the problems of low tumor immunogenicity, tumor tissue immunosuppressive microenvironment limitation, complex process, etc., achieve good temperature-sensitive gelation performance, and improve tumor immunotherapy. , prepare a simple effect

Pending Publication Date: 2021-12-24
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current tumor vaccine therapy mainly has the following obstacles: 1) low immunogenicity of tumors; 2) tumor-associated antigens or tumor neoantigens vary greatly in different types of tumors or in different patients with the same tumor type
In recent years, personalized vaccines targeting patient-specific antigens have been developed, but complex antigen identification is required, which is complicated, expensive, and only beneficial to some patients; 3) Immunosuppressive microenvironment limitations of tumor tissue

Method used

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  • Injectable drug-loaded temperature-sensitive hydrogel capable of enhancing anti-tumor immunity and preparation and application thereof
  • Injectable drug-loaded temperature-sensitive hydrogel capable of enhancing anti-tumor immunity and preparation and application thereof
  • Injectable drug-loaded temperature-sensitive hydrogel capable of enhancing anti-tumor immunity and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1: Preparation of in vivo injectable drug-loaded thermosensitive hydrogel PLGA-PEG-PLGA

[0056] (1) Dry the azeotropic device in an oven at 95°C, add 7.530g of double-terminal hydroxyl PEG (1500Da) and 60mL of anhydrous toluene into the container, and distill at 135°C under atmospheric pressure to azeotropically remove water; quickly connect the container after the water removal is completed Fill the suction head with nitrogen, put it into a 60°C oil bath, and depressurize and remove water overnight with a vacuum pump;

[0057] (2) Add D, L-LA and GA to the dried container respectively, freeze and pump three times, then put it into an oil bath at 60°C, and depressurize and remove water overnight with a vacuum pump;

[0058] (3) Transfer the PEG, D, L-LA and GA after dehydration overnight under reduced pressure to the glove box, dissolve the dehydrated PEG, 16.790gD, L-LA and 0.912g GA at 130°C for 0.5h, add 50mg Catalyst stannous octoate (0.2wt% of the reactio...

Embodiment 2

[0062] Embodiment 2: PLGA-PEG-PLGA amphiphilic copolymer number-average molecular weight, molecular weight distribution, phase transition temperature measurement

[0063] (1) figure 1 For the PLGA-PEG-PLGA amphiphilic polymer prepared in Example 1 in CDCl 3 The NMR results in (ie 1 HNMR figure), it can be seen that the resonance peaks of various proton signals in the expected structure can be well assigned, and the split and integrated area of ​​each peak are also consistent with the expected structure. 1 The average number average molecular weight of the PLGA-PEG-PLGA triblock copolymer is 5200 calculated from the integral area of ​​the three peaks at 4.80, 3.63 and 1.55ppm in the H NMR spectrum.

[0064] (2) figure 2 GPC trace of the PLGA-PEG-PLGA amphiphilic copolymer prepared for Example 1. By GPC (such as figure 2 ) It can be known that the retention time of the PLGA-PEG-PLGA amphiphilic polymer prepared in Example 1 is 32.59min. Mn is 6370, Mw is 7340, molecular ...

Embodiment 3

[0067] Example 3: Preparation of injectable drug-loaded thermosensitive hydrogel

[0068] (1) Dissolve 10.1 mg of R848 in 200 μL of methanol to obtain a methanol solution of R848;

[0069] (2) 5.1 mg of MIT was dissolved in 200 μL of water to obtain MIT aqueous solution;

[0070] (3) Add the above-mentioned methanol solution of R848 and MIT aqueous solution to 14 mL of 5 wt% PLGA-PEG-PLGA (copolymer prepared in Example 1) aqueous solution, stir for 2 hours, remove the methanol, and freeze-dry;

[0071] (4) Add water to the freeze-dried product of step (3), so that the final mass concentration of PLGA-PEG-PLGA amphiphilic copolymer is 14wt%, and stir on ice for 24 hours to form a uniformly dispersed drug-loaded sol (flowing state) .

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Abstract

The invention belongs to the technical field of medicines, and discloses injectable drug-loaded temperature-sensitive hydrogel capable of enhancing anti-tumor immunity and preparation and application thereof. The injectable drug-loaded temperature-sensitive hydrogel capable of enhancing the anti-tumor immunity is mainly prepared from a PLGA-PEG-PLGA amphiphilic copolymer and a drug, and the drug is R848 and MIT or the drug is a cyclodextrin inclusion compound of the R848 and MIT. The invention also discloses a preparation method of the drug-loaded temperature-sensitive hydrogel. The injectable drug-loaded temperature-sensitive hydrogel can improve the enrichment of the drug at a tumor site and continuously and slowly release the drug; meanwhile, the TAMs are repolarized, the ICD effect is induced, the tumor immune microenvironment is jointly regulated and controlled, system immunity can be initiated by local administration, tumor immunotherapy can be improved, and a good anti-tumor effect is achieved. The injectable drug-loaded temperature-sensitive hydrogel is used for preparing tumor vaccine preparations and / or tumor immunotherapy drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an injectable drug-loaded temperature-sensitive hydrogel and its preparation and application. The application of the injectable drug-loaded thermosensitive hydrogel in the preparation of tumor vaccine preparations enhances tumor immunotherapy. Background technique [0002] Compared with traditional therapies, tumor immunotherapy, which stimulates or trains the immune system to recognize and kill tumor cells, is a promising treatment strategy. Tumor vaccine is one of the main strategies of tumor immunotherapy. It has great potential in triggering antigen-specific immune response and long-term immune memory. Hundreds of tumor vaccines are in different stages of clinical trial research. However, current tumor vaccine therapy mainly has the following obstacles: 1) low immunogenicity of tumors; 2) tumor-associated antigens or tumor neoantigens are quite different in diff...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K31/4745A61K47/34A61K47/69A61P35/00A61P37/04C08G63/664A61K31/136
CPCA61K9/06A61K47/34A61K9/0024A61K31/4745A61K31/136A61K47/6951C08G63/664A61P35/00A61P37/04A61K2300/00
Inventor 杜金志刘容巫佳思张京扬
Owner SOUTH CHINA UNIV OF TECH
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