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A temperature-sensitive nano drug preparation for in-depth delivery of tumor drugs and its preparation method and application

A tumor drug and nano-drug technology, applied in the field of biomedicine, can solve the problem that nano-drug carriers are difficult to penetrate deeply, and achieve the effects of large-scale production, improved targeting, and easy access.

Active Publication Date: 2021-10-08
XIDIAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Nanoparticles of 50-100nm have a strong EPR effect, but after the nanocarriers of this size are enriched near the tumor blood vessels through blood circulation, due to the densely arranged outer layer of stromal cells and the higher fluid osmotic pressure inside the solid tumor , making it difficult for nano-drug carriers to penetrate deeply into solid tumors

Method used

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  • A temperature-sensitive nano drug preparation for in-depth delivery of tumor drugs and its preparation method and application
  • A temperature-sensitive nano drug preparation for in-depth delivery of tumor drugs and its preparation method and application
  • A temperature-sensitive nano drug preparation for in-depth delivery of tumor drugs and its preparation method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0050] 1.1. Thermosensitive polymer chain PCL with chemotherapeutic drugs 4000 - Preparation of Azo-PAMAM / Drug

[0051] 1). Weigh the hydrophobic polymer chain PCL 4000 15mg, temperature-sensitive intermediate VA-057 25mg, condensing agent EDC15mg and DMAP 5mg were dissolved in low-temperature tetrahydrofuran respectively, and then mixed and reacted for 12 hours under low-temperature conditions, and then dialyzed with a dialysis bag with a molecular weight cut-off of 1000Da, and lyophilized. PCL was obtained as a white solid 4000 -Azo-COOH;

[0052] 2). Weigh the chemotherapeutic drug cisplatin Pt(NH 3 ) 2 Cl 2 Dissolve 100 mg in 2.5 mL of water, add 3.5 mL of 30% w / v hydrogen peroxide solution, react at 50°C for 1 h, then wash with acetone and ether three times alternately, filter with suction and dry to obtain bright yellow solid Pt( NH 3 ) 2 Cl 2 (OH) 2 , the yield is 49%;

[0053] 3). Weigh the Pt(NH 3 ) 2 Cl 2 (OH) 2 Dissolve 50 mg in 4 mL of anhydrous DM...

Embodiment 2

[0059] 2.1 Verification of temperature sensitivity of aliphatic azo intermediate Azo-linker

[0060] Take 4 equal amounts of 25 mg of aliphatic azo intermediate VA-057, dissolve them in 5 mL of water respectively, add 0.2 mL of free radical indicator methylene blue, and heat at different temperatures for 15 min to obtain the following: Figure 7 The results shown show that as the temperature increases, the aliphatic azo intermediate VA-057 has a faster thermal response speed, so it can be proved that the nanoparticles prepared in Example 1 have a faster thermal response speed.

[0061] 2.2 Therapeutic effect at the cellular level of temperature-sensitive nanomedicine formulations for deep delivery of tumor drugs

[0062] In order to verify the therapeutic effect of the temperature-sensitive nanomedicine preparations for the deep delivery of tumor drugs at the cellular level, the following five probes were synthesized: NN-PAMAM, NN-PAMAM@IR780, NN-PAMAM / Pt, NN-PAMAM / Pt@IR780 ...

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Abstract

The invention belongs to the technical field of biomedicine, and in particular relates to a temperature-sensitive nano-medicine preparation for in-depth delivery of tumor drugs, a preparation method and application thereof. Under the irradiation of near-infrared light (for example, under the irradiation of laser with a wavelength of 650-900nm), the temperature-sensitive nano-medicine preparation provided by the present invention for in-depth delivery of tumor drugs generates mild photothermal, so that the temperature-sensitive intermediate Azo- The linker breaks and generates non-oxygen-dependent free radicals, which have the effects of photothermal therapy (PTT) and photodynamic therapy (PDT). In addition, the mild photothermal energy causes the enrichment of the drug preparation in tumor blood vessels, improves the targeting of the drug preparation, and thus increases the enrichment amount of chemotherapy drugs in the tumor site.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a temperature-sensitive nano-medicine preparation for in-depth delivery of tumor drugs, a preparation method and application thereof. Background technique [0002] Chemotherapy is the first choice for cancer patients in clinical practice, but it faces severe challenges such as poor solubility and poor targeting of small molecule chemotherapeutic drugs, resulting in large systemic toxic and side effects, severe side effects, low drug accumulation in tumor sites, and poor curative effect. challenge. It has been reported that nanocarriers can effectively improve the targeting, stability and loading rate of chemotherapy drugs. Therefore, the use of nanocarriers to assist chemotherapy not only increases the solubility of chemotherapy drugs, but also enhances the EPR effect of tumors, thereby improving the drug-loaded nanoparticles. The amount of enrichment at the tumo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/59A61K41/00A61K45/00A61K9/00A61P35/00C08G81/00
CPCA61K9/0009A61K41/0042A61K41/0052A61K41/0057A61K45/00A61K47/59A61P35/00C08G81/00A61K2300/00
Inventor 王忠良常湾湾张瑞丽王中嫡王琳琳黄慧敏贾茜乔晁强陈柏行
Owner XIDIAN UNIV
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