An acid-responsive nanometer micelle for drug loading, a preparation method and an application thereof

A nano-micelle, acid technology, applied in the field of acid-responsive nano-micelles and their preparation, can solve the problems of unsatisfactory effect, killing tumor cells, slow drug release, etc., to enhance anti-tumor effect, improve effect, increase tissue permeability effect

Active Publication Date: 2019-01-11
THE SECOND AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this way, due to the slow release of drugs, the nano-drugs cannot achieve satisfactory effects after being taken up by cells, and the concentration of free drugs is not enough to kill tumor cells, and may induce drug resistance, leading to treatment failure

Method used

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  • An acid-responsive nanometer micelle for drug loading, a preparation method and an application thereof
  • An acid-responsive nanometer micelle for drug loading, a preparation method and an application thereof
  • An acid-responsive nanometer micelle for drug loading, a preparation method and an application thereof

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preparation example Construction

[0041] In some embodiments, a method for preparing ultra-sensitive slightly acidic environment-responsive nanomicelles is provided, comprising the following steps:

[0042] S1. Synthesis of aminated PEG-NH with PEG-OH as raw material 2 ;

[0043] S2. Aminated PEG-NH 2 As the initiator, in freshly distilled CHCl 3 Initiate ring-opening polymerization of BLA-NCA in anhydrous DMF mixed solvent to obtain PEG-PBLA;

[0044] S3. Using PEG-PBLA as raw material, add DIP and DBA (1:0; 3:1; 1:1; 1:3; 0:1) in anhydrous DMSO according to five different molar ratios for ammonolysis to obtain PEG-PAsp (DIP / DBA).

[0045] In some embodiments, S1 uses PEG-OH as raw material to synthesize PEG-NH 2 The specific steps are: the PEG-OH with freshly distilled CHCl 3 After dissolving, add DMAP, triethylamine and p-toluenesulfonyl chloride at 0°C, stir at room temperature for 12 hours, precipitate in a large amount of ether, and filter and dry. Add the solid to a large amount of ammonia water ...

Embodiment 1

[0054] An embodiment of the acid-responsive nanomicelle used for drug loading in the present invention is a two-block polymer formed by the self-assembly of a hydrophilic block and a hydrophobic block; wherein, the hydrophilic block is PEG, and the hydrophobic block is PEG. The neutral block is PAsp(DIP / DBA); the preferred molecular weight of PEG is 2kDa, and the preferred molecular weight of PAsp(DIP / DBA) is 10kDa.

[0055] An embodiment of the anti-tumor nano-medicine in the present invention is composed of the above-mentioned nano-micelle loaded with doxorubicin and / or SPIO; wherein, the particle size of the anti-tumor nano-medicine is 130.5±8.0nm.

[0056] An embodiment of the preparation method of the anti-tumor nano-medicine in the present invention includes the following steps: using an emulsification method to ultrasonically induce the assembly of the above-mentioned nano-micelle, doxorubicin and SPIO to prepare an anti-tumor nano-drug visualized by magnetic resonance. ...

Embodiment 2

[0057] The synthesis of embodiment 2 block polymers (i.e. nano micelles)

[0058] A kind of embodiment of the preparation method of nano-micelle of the present invention, the synthetic route of block polymer (nano-micelle) is as follows figure 1 As shown, it specifically includes the following steps:

[0059] First, sulfonated PEG was synthesized from PEG-OH. Specifically, 7.0 g of PEG-OH was first mixed with 50 mL of anhydrous CHCl 3 Dissolve, then add 43mg DMAP, 0.73mL triethylamine and 1.0g p-toluenesulfonyl chloride at 0°C, stir and react at room temperature for 12 hours, then precipitate the reaction solution in a large amount of anhydrous ether (more than 8 times the volume of the reaction solution) ), filtered to obtain a solid, and obtained a solid sulfonated PEG after vacuum drying;

[0060] Then, the solid was added to a large amount of ammonia water (23%-28%), sealed, stirred for at least 5 days, concentrated, and washed with CHCl 3 After extraction, add dilute ...

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Abstract

The invention discloses an acid-responsive nanometer micelle for drug loading, a preparation method and an application thereof. The nano-micelles were self-assembled from hydrophilic segment polyethylene glycol (PEG) and hydrophobic segment pH-sensitive polyaspartyl diisopropylethylenediamine/di-n-butylethylenediamine (PAsp (DIP/DBA)). The nano-micelles can prolong the drug circulation time, aggregate in the tumor site, increase the local drug concentration, and respond to the micro-acid environment of the tumor tissue. As a drug carrier of stimulation response, the nano-micelles can rapidly release the loaded chemotherapeutic drug adriamycin in the tumor site, and play a significant anti-tumor effect. At the same time, the nano-micelles loaded with magnetic resonance contrast agent superparamagnetic iron oxide can be used for tumor magnetic resonance imaging and monitoring drug uptake and aggregation. This method utilizes nano-drug aggregation at tumor site and acid responsiveness ofcarrier to realize rapid drug release to improve tumor therapeutic effect, and endows nano-micellar MRI visualization function, which provides a promising innovative strategy for cancer diagnosis andtreatment, and has broad application prospects.

Description

technical field [0001] The invention relates to the technical field of drug carriers, in particular to an acid-responsive nano-micelle for drug loading and its preparation method and application. Background technique [0002] Chemotherapy is one of the most important treatment methods for tumors, and it is often used in combination with other treatment methods to maximize the efficiency of killing tumor cells and improve the survival rate of patients. However, chemotherapy is a systemic treatment, and the selectivity of chemotherapeutic drugs is not strong. While killing tumor cells, it will inevitably damage the normal cells of the body, thereby bringing obvious toxic and side effects. Moreover, most chemotherapeutic drugs are hydrophobic drugs with low solubility, short half-life and low bioavailability. Therefore, how to improve the bioavailability of drugs, enhance the effect of drugs and reduce the toxic and side effects of drugs is an important issue for cancer chemot...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/34A61K31/704A61P35/00A61K49/18A61K49/12
CPCA61K47/34A61K49/126A61K49/1809A61P35/00A61K9/1075A61K31/704
Inventor 朱康顺帅心涛蔡明岳李博林立腾黄敬君
Owner THE SECOND AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV
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