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a kind of ga 3+ /pda targeted synergistic antibacterial nanomaterials, their preparation and application

A composite material and polymerization reaction technology, applied in the field of antibacterial materials, can solve the problems of untargetable release, no targeting, and uncontrollable subcutaneous and in vivo infection, so as to improve the killing effect and reduce the effect of toxicity

Active Publication Date: 2020-11-17
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Although Ga 3+ has remarkable antibacterial properties, but its practical application in anti-infection is limited by two major issues
First is Ga 3+ Toxicity problem: the minimum inhibitory concentration of gallium nitrate against common bacteria is about 36 μM, which is already obviously toxic to mammalian cells
Chelating agents such as citric acid, maltol, and protoporphyrin are often used to chelate Ga 3+ , to increase the Ga 3+ stability, reducing the Ga 3+ Precipitation caused by hydrolysis, but these chelates are not targeted and cannot make Ga 3+ Targeted release at the site of infection
Ga 3+ Doped in hydrogels and wound dressings to control pathogenic bacterial infections on the body surface, but cannot control subcutaneous and internal infections

Method used

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  • a kind of ga  <sup>3+</sup> /pda targeted synergistic antibacterial nanomaterials, their preparation and application
  • a kind of ga  <sup>3+</sup> /pda targeted synergistic antibacterial nanomaterials, their preparation and application
  • a kind of ga  <sup>3+</sup> /pda targeted synergistic antibacterial nanomaterials, their preparation and application

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preparation example Construction

[0041] A kind of polydopamine composite material (also expressed as Ga in the present invention) of chelated gallium ion provided by the invention 3+ / PDA nanocomposite) preparation method, gallium ions are chelated to dopamine under acidic conditions, then induce dopamine self-polymerization to form polydopamine nanoparticles chelating gallium ions, specifically comprising the following steps:

[0042] (1) Mix the aqueous solution of dopamine or dopamine salt with the aqueous solution of gallium salt, and adjust the pH of the mixed system to 2-4, so that the gallium salt and dopamine in the mixed system undergo a chelation reaction, and obtain the chelated mixed system;

[0043] (2) adding an oxidizing agent to the mixed system after chelation, so that the dopamine in the mixed system undergoes a polymerization reaction to obtain a mixed system after dopamine polymerization;

[0044] (3) Add a precipitating agent to the mixed system after dopamine polymerization, so that the...

Embodiment 1

[0074] Ga 3+ / PDA nanoparticles preparation:

[0075] Dissolve dopamine hydrochloride and gallium nitrate in a certain volume of deionized water at a molar ratio of 1:1-3, stir magnetically for about 30 minutes, and then add 50-500 microliters of 30% hydrogen peroxide solution, at pH=3, 15- Magnetic stirring was carried out at 40°C for 12-48 hours. After the reaction, add twice the volume of absolute ethanol, centrifuge at 14,000g for 10-30min, and wash the precipitate with 50mM Tris-HCl (pH=8.5) three times, then wash twice with deionized water and dry to constant weight You can get the finished product.

[0076] figure 1 a is H 2 o 2 Induced self-aggregation of dopamine to produce Ga 3+ / PDA nanoparticles (Ga 3+ / PDA) schematic diagram; figure 1 b is Ga 3+ Schematic diagram of the pH-responsive release. When Ga 3+ When / PDA is in a normal weakly alkaline physiological environment, Ga 3+ Tightly chelated with dopamine, Ga 3+ not easily from Ga 3+ / PDA nanopartic...

Embodiment 2

[0081] Ga 3+ / Characteristics of the surface charge of PDA nanoparticles changing with pH

[0082] Determination of Ga using a particle size analyzer 3+ / PDA nanoparticles surface potential, by Figure 5 It can be seen that its surface potential has the characteristics of pH-responsive change: at pH=7.4, its surface potential value is -7.43±0.74mV, and at pH=6.5, its surface potential value reverses to 13.67±1.49mV. When it was further reduced to 5.5, the surface potential value further increased to 21.49±2.76mV. This is due to the deprotonation of catechol groups in weak alkaline, which makes the nanoparticles negatively charged, and when the pH is reduced to 6.5 and 5.5, the catechol and amine groups are protonated, making the nanoparticles negatively charged. Positively charged. The results showed that the prepared Ga 3+ / PDA surface potential can realize the reversal of surface potential in the range of pH 7.4-6.5, which can ensure the obvious Ga from pH 7.4 to 6.5 3...

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Abstract

The invention belongs to the field of an antibacterial material, and particularly relates to a Ga<3+> / PDA targeted co-antibacterial nanometer material, and preparation and application thereof. Under acid conditions, gallium ions take a chelation reaction with PDA; and then, under the condition that an oxidizing agent exists, dopamine chelated with the gallium ions is induced to take an auto polymerization to obtain a novel targeted co-antibacterial nanometer material which shows the obvious surface charge reversal in a narrow pH range (the pH is from 7.4 to 6.5) so as to control the Ga<3+> chelation and dissociation in the narrow pH range and simultaneously has the Ga<3+> and heat sterilization effects, so that the technical problems that in the antibacterial application of using the gallium ions in the prior art, the toxicity problem exists, hydrolysis easily occurs, and the bioavailability and the antibacterial efficiency are reduced are solved.

Description

technical field [0001] The invention belongs to the field of antibacterial materials, more specifically, relates to a Ga 3+ / PDA targeted synergistic antibacterial nanomaterials, their preparation and application. Background technique [0002] Bacterial infectious diseases are the most common diseases worldwide, accounting for 18%-21% of all diseases. Antibiotics are the main drug for the treatment of bacterial infections, which can greatly reduce the mortality rate of patients. However, the large-scale application of antibiotics also promotes the gradual increase of bacterial resistance to antibiotics. The emergence of drug-resistant bacteria and even multi-drug-resistant bacteria has led to The control effect on drug-resistant bacteria is reduced, and there is even a dangerous situation where no drug is available. The development of new antibacterial materials is an important part of controlling drug-resistant bacterial infections and ensuring the health of the populatio...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K33/24A61K9/51A61K47/34A61P31/04
CPCA61K9/5146A61K33/24A61K41/0052A61P31/04A61P35/00A61K2300/00
Inventor 吕斌戚俊峰陈思怡
Owner HUAZHONG UNIV OF SCI & TECH