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Tumor microenvironment stimulation degradable amphiphilic block HPMA (hydroxypropyl methacrylate) polymer delivery system and preparation method thereof

A tumor microenvironment and amphiphilic block technology, applied in the field of amphiphilic block HPMA polymer drug delivery system, can solve problems such as unfavorable industrial scale-up, cumbersome purification process, etc., to maintain stability, effective aggregation, good biological Compatibility and effect of antitumor effect

Active Publication Date: 2017-04-26
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the preparation of peptide dendrimers requires step-by-step synthesis and tedious purification processes, which is not conducive to industrial scale-up

Method used

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  • Tumor microenvironment stimulation degradable amphiphilic block HPMA (hydroxypropyl methacrylate) polymer delivery system and preparation method thereof
  • Tumor microenvironment stimulation degradable amphiphilic block HPMA (hydroxypropyl methacrylate) polymer delivery system and preparation method thereof
  • Tumor microenvironment stimulation degradable amphiphilic block HPMA (hydroxypropyl methacrylate) polymer delivery system and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0062] The tumor microenvironment stimulates the degradable amphiphilic block HPMA polymer drug delivery system. The drug delivery system is a conjugate of HPMA polymer, cathepsin B substrate GFLG and small molecule drug gemcitabine. The specific structure is as follows:

[0063]

[0064] Where: m=0-4;

[0065] n=270-320;

[0066] o=5-12;

[0067]

Embodiment 2

[0069] This embodiment is on the basis of embodiment 1:

[0070] The average degree of polymerization of the drug delivery system is m=0, n=260, o=5.

[0071] The average molecular weight of the drug delivery system is 80KDa.

Embodiment 3

[0073] This embodiment is on the basis of embodiment 1:

[0074] R: -N 3 .

[0075] The average degree of polymerization of the drug delivery system is m=0.4, n=280, o=7.

[0076] The average molecular weight of the drug delivery system is 90KDa.

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Abstract

The invention provides a tumor microenvironment stimulation degradable amphiphilic block HPMA (hydroxypropyl methacrylate) polymer delivery system which is a conjugate of HPMA polymer, cathepsin B substrate GFLG, and small-molecular drug gemcitabine; the nano delivery system formed by self-assembly of the amphiphilic block conjugate has enzyme responsive degrading capacity and drug release capacity, gemcitabine is delivered by being conjugated to the amphiphilic block HPMA polymer skeleton, the molecular weight of the system is relatively high, the system may effectively collect at a tumor part, has good biocompatibility and antitumor effect, and by introducing near-infrared fluorescent probe Cy5.5, self-tracing capacity is imparted to the system.

Description

technical field [0001] The invention belongs to the technical field of medical biopolymer materials, and relates to a nanometer drug delivery system, in particular to a degradable amphiphilic block HPMA polymer drug delivery system stimulated by a tumor microenvironment. Background technique [0002] The treatment of clinical breast cancer faces many challenges. The use of drug delivery systems that last longer in vivo, have higher tumor specificity, and lower side effects is expected to further improve the treatment of breast cancer. After the antineoplastic drug gemcitabine (GEM) enters the systemic circulation, it is easily metabolized into an inactive uracil intermediate (2'-deoxy-2'-2'-difluorocytidine [dFdU]) in the body and is quickly eliminated. Therefore, its stability needs to be further improved. In order to solve the challenges faced by the treatment, the nano-drug delivery system uses the enhanced osmotic retention effect (EPR) effect unique to solid tumor tiss...

Claims

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Application Information

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IPC IPC(8): A61K47/58A61K47/65A61K47/69A61K49/00
CPCA61K49/0045A61K49/0054A61K49/0056A61K49/0093
Inventor 罗奎段振宇张艳红
Owner SICHUAN UNIV
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