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PH responsive nanometer carrier as well as preparation method and application thereof

A nanocarrier and nanoparticle technology, which is applied in the directions of non-active ingredient medical preparations, medical preparations containing active ingredients, and pharmaceutical formulas, can solve the problem of inability to efficiently transport large-sized biological macromolecules such as proteins, etc. Achieve the effect of avoiding early leakage and release

Active Publication Date: 2019-04-02
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The invention solves the technical problem that mesoporous silica nanoparticles cannot efficiently carry large biological macromolecules such as proteins, and realizes the controllable release of large biological macromolecules such as proteins under a specific pH environment

Method used

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  • PH responsive nanometer carrier as well as preparation method and application thereof
  • PH responsive nanometer carrier as well as preparation method and application thereof
  • PH responsive nanometer carrier as well as preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0047] A method for preparing mesoporous silica nanoparticles for pH-responsive controlled release of protein drugs, the preparation method mainly comprising the following steps:

[0048] (1) Reaction of 3-aminopropyltriethoxysilane with 2,3-dimethylmaleic anhydride to obtain a silane coupling agent containing an acid-sensitive amide bond. Specifically, 3-aminopropyltriethoxysilane is added to the dry tetrahydrofuran solution, triethylamine is added to adjust the pH of the solution to be 8.5, and 2,3-dimethylmaleic anhydride is added in an amount equal to that of the substance, at 25 °C for 24 hours.

[0049] (2) Using ethyl acetate as the pore-enlarging agent, using cetyltrimethylammonium bromide and the pore-enlarging agent as the template, self-assembled to form a mesoporous structure, the silicon source was hydrolyzed and condensed under alkaline conditions, and then The template is removed to obtain mesoporous silica nanoparticles. Specifically, dissolve 100 mg of cetyl...

Embodiment 2-6

[0056] Preparation method of mesoporous silica nanoparticles with different pH response thresholds. The preparation method of mesoporous silica nanoparticles is the same as that of Example 1. Silane coupling agents containing different acid-sensitive chemical bonds undergo hydrolysis condensation reaction with mesoporous silica nanoparticles to obtain mesoporous silica nanoparticles with different pH response thresholds. Table 1 lists the pH response thresholds of several different acid-sensitive chemical bonds.

[0057] Table 1

[0058]

Embodiment 7

[0060] pH-responsive mesoporous silica nanoparticles surface charge inversion assay.

[0061] The mesoporous silica nanoparticles containing acid-sensitive amide bonds prepared in Example 1 were dispersed in 20 mL of buffer solutions with different pH values ​​(pH=6.8, 7.4), and 1 mL of the solutions were taken out at certain time intervals, and used Real-time monitoring of the zeta potential of pH-responsive mesoporous silica nanoparticles by laser particle size analyzer ( figure 2 ). The results showed that the surface potential of the mesoporous silica nanoparticles containing acid-sensitive amide bonds increased continuously in the buffer solution of pH=6.8, and the transition from negative to positive was realized within 30 minutes. However, in the buffer solution with pH=7.4, although the potential of the mesoporous silica nanoparticles increases slightly, the negative charge remains throughout the observation time. It shows that the mesoporous silica nanoparticles ha...

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Abstract

The invention discloses a pH responsive nanometer carrier as well as a preparation method and application thereof, and belongs to the field of medicine delivery. Biomacromolecule is loaded to a pore canal of pH responsive mesoporous silica nanoparticles, a hole plugging agent is used for plugging the pore canal of the mesoporous silica nanoparticles, and the pH responsive mesoporous silica nanoparticles are mesoporous silica nanoparticle surface grafted acidic sensitivity molecules, wherein the diameter of the nanoparticle pore canal is 5-50nm. Under the condition that the pH value is smallerthan or equal to threshold, an acidic sensitivity chemical bond is ruptured, and charge on the surfaces of the nanoparticles is turned into positive charge from negative charge; and under the action of electrostatic repulsion, the hole plugging agent with the positive charge is separated from the surfaces of the mesoporous silica nanoparticles, the pore canal is exposed, and the biomacromolecule is quickly released. The pH responsive nanometer carrier can effectively solve the problems that the biomacromolecule leaks before arriving at target cells or cannot be controllably released under thespecific condition in cells, and controlled release under the specific pH condition of the loaded biomacromolecule is realized.

Description

technical field [0001] The invention belongs to the field of drug delivery, and more specifically relates to a pH-responsive nano-carrier for controlled release of biomacromolecules and its preparation method and application, which can rapidly and intelligently release biomacromolecules when the pH is less than or equal to a threshold value. Background technique [0002] Biomacromolecules include protein drugs, polysaccharide drugs, nucleic acid drugs, etc., and are mostly used to treat major diseases such as tumors, cardiovascular and cerebrovascular diseases, immune diseases, hepatitis, neurodegenerative diseases, and bleeding. Compared with chemically synthesized small molecule drugs, biomacromolecular drugs have the advantages of high activity, strong specificity, less adverse reactions, clear biological functions, and safety and reliability. However, the application of biomacromolecules still faces many difficulties, such as poor stability, poor membrane permeability, s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/04A61K47/18A61K47/16A61K47/02A61K38/41A61P35/00A61P9/00A61P37/02A61P1/16A61P31/14A61P31/20A61P25/28A61P7/04
CPCA61K9/5115A61K9/5123A61K9/5192A61K38/41A61P1/16A61P7/04A61P9/00A61P25/28A61P31/14A61P31/20A61P35/00A61P37/02
Inventor 朱锦涛郭晨李钰策蒋皓张连斌
Owner HUAZHONG UNIV OF SCI & TECH
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