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Ga<3+>/PDA targeted co-antibacterial nanometer material, and preparation and application thereof

A composite material and polymerization technology, applied in the field of antibacterial materials, can solve the problems of untargeted release, no targeting, uncontrollable subcutaneous and in vivo infection, etc., to achieve the effect of improving the killing effect and reducing the toxic effect

Active Publication Date: 2020-02-14
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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  • Ga&lt;3+&gt;/PDA targeted co-antibacterial nanometer material, and preparation and application thereof
  • Ga&lt;3+&gt;/PDA targeted co-antibacterial nanometer material, and preparation and application thereof
  • Ga&lt;3+&gt;/PDA targeted co-antibacterial nanometer material, and preparation and application thereof

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preparation example Construction

[0041] The invention provides a polydopamine composite material chelating gallium ions (also expressed as Ga in the invention) 3+ / PDA nanocomposite material), in which gallium ions are chelated to dopamine under acidic conditions, and then dopamine is induced to self-polymerize to form gallium ion-chelated polydopamine nanoparticles, which specifically includes 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 to obtain a chelated mixture system;

[0043] (2) Adding an oxidizing agent to the chelated mixed system to cause the dopamine in the mixed system to undergo 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 polydopamine complex of che...

Embodiment 1

[0074] Ga 3+ / PDA Nanoparticle Preparation:

[0075] Dissolve dopamine hydrochloride and gallium nitrate in a certain volume of deionized water at a molar ratio of 1:1-3. After magnetic stirring for about 30 minutes, add 50-500 microliters of 30% hydrogen peroxide solution at pH=3,15- The reaction was stirred magnetically at 40°C for 12-48h. After the reaction, add double volume of absolute ethanol, centrifuge for 10-30min under 14000g centrifugal force, and wash the precipitate with 50mM Tris-HCl (pH=8.5) three times, then wash with deionized water twice and then dry to constant weight You can get the finished product.

[0076] figure 1 a is H 2 O 2 Inducing dopamine self-polymerization to prepare Ga 3+ / PDA Nanoparticles (Ga 3+ / PDA) schematic diagram; figure 1 b is Ga 3+ Schematic diagram of pH-responsive release. When Ga 3+ / PDA is in a normal weak alkaline physiological environment, Ga 3+ Chelate tightly with dopamine, Ga 3+ Not easy from Ga 3+ / PDA nanoparticles are dissoci...

Embodiment 2

[0081] Ga 3+ / PDA Nanoparticle Surface Charge Variation Characteristics with pH

[0082] Determination of Ga using particle size analyzer 3+ / PDA nanoparticle surface potential, by Figure 5 It can be seen that its surface potential has the characteristics of pH responsive change: when pH=7.4, its surface potential value is -7.43±0.74mV, and when pH=6.5, its surface potential value is inverted, which is 13.67±1.49mV. When it is further reduced to 5.5, its surface potential value further increases, reaching 21.49±2.76mV. This is due to the deprotonation of the catechol groups when weakly alkaline, making the nanoparticles negatively charged, and when the pH drops to 6.5 and 5.5, the catechol and amine groups are protonated, making the nanoparticles Positively charged. The results show that the prepared Ga 3+ The surface potential of / PDA can be reversed in the range of pH 7.4-6.5, and it can ensure that obvious Ga is present at pH from 7.4 to 6.5 3+ Chelation and dissociation tra...

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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, and 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 drugs for the treatment of bacterial infections, which can greatly reduce the mortality of patients. However, the large-scale application of antibiotics has also promoted the gradual increase of the resistance of bacteria to antibiotics. The emergence of resistant bacteria or even multi-drug resistant bacteria has led to the existing antibiotics. The control effect of drug-resistant bacteria is reduced, and there is even a dangerous situation of no medicine available. The development of new antibacterial materials is an important part of controlling the infection of drug-resistant bacteria and protectin...

Claims

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Application Information

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