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Modified albumin nano particle capable of ultrasonically releasing NO gas as well as preparation method and application of modified albumin nano particle

A technology of albumin nanoparticles and nanoparticles, which is applied in the field of new biomedical materials, can solve the problems of unconsidered albumin modification, uncontrollable release of drugs, and low drug release, which is conducive to large-scale preparation and good dispersion , strong penetrating effect

Inactive Publication Date: 2021-11-09
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In short, the existing technology has the problem that albumin nanoparticles cannot controlly release drugs under physiological conditions, and can only release drugs slowly under endogenous stimuli such as acidity or reduction, while light-controlled release has poor tissue penetration, resulting in Defects such as low drug release need to be solved urgently
[0005] Although the Chinese invention patent (application) CN202010186222.2 discloses an albumin nanoparticle that can be activated by ultrasound to release drugs, its preparation method and application, it uses an azo cross-linking agent and carries a chemotherapeutic drug for ultrasonic release, but the patent uses The albumin is unmodified albumin, and the modification of albumin is not considered, so it does not involve the release of NO signal molecules

Method used

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  • Modified albumin nano particle capable of ultrasonically releasing NO gas as well as preparation method and application of modified albumin nano particle
  • Modified albumin nano particle capable of ultrasonically releasing NO gas as well as preparation method and application of modified albumin nano particle
  • Modified albumin nano particle capable of ultrasonically releasing NO gas as well as preparation method and application of modified albumin nano particle

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Experimental program
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Effect test

Embodiment 1

[0037] Preparation of modified albumin with reduced disulfide bonds

[0038] Dissolve 5g of bovine serum albumin powder in 100g of ultrapure water, and place a magnetic stirrer at 200-500 rpm for 1 hour. Take 6.975g albumin aqueous solution, add 284μl 2-mercaptoethanol, use 1M NaOH to adjust the pH value of the solution to 8, and stir at room temperature overnight. Adjust the pH value of the solution to 3 with 1M HCl, dialyze with a dialysis bag with a molecular weight cut-off of 3500Da for 24 hours, and adjust the pH to 5 during the dialysis process to obtain a modified albumin BSA-SH solution with reduced disulfide bonds.

[0039] Gained modified bovine serum albumin ultraviolet-visible spectrum characterization is as follows figure 1 , The free sulfhydryl group obtained by reducing the disulfide bond in the modified bovine serum albumin reacts with the total sulfhydryl reagent, and has an absorption peak at a wavelength of 420nm in the ultraviolet-visible spectrum.

Embodiment 2

[0041] Preparation of modified albumin containing -SNO group capable of releasing NO gas

[0042] Take 5 mL of the BSA-SH solution prepared in Example 1, add 37 μl of tert-butyl nitrite to it, stir and react at room temperature for 12 h, dialyze with a dialysis bag with a molecular weight cut-off of 3500 Da for 24 h, and obtain -SNO Groups of modified albumin in BSA-SNO solution.

Embodiment 3

[0044] Modified bovine serum albumin-based nanoparticles (BSASNO) were prepared by desolvation method. In principle, take 5ml of the BSA-SNO solution prepared in Example 2, adjust the pH to 7 with 0.1mol / L NaOH, add 2.5mL of absolute ethanol dropwise at a constant rate of 2.5mL / min, and the desolvation process is completed Afterwards, the reaction was continued overnight at 37° C. in the dark to obtain a stable solution of modified albumin nanoparticles. Centrifuge the obtained stable modified albumin nano solution at 12000 rpm, wash the precipitate with deionized water, repeat three times, and finally disperse with a certain amount of deionized water, freeze-dry to obtain modified bovine serum albumin BSASNO nanoparticles.

[0045] The transmission electron microscope image of the obtained modified albumin BSASNO nanoparticles that can release NO gas by ultrasonic figure 2 , BSASNO nanoparticles have a radius of about 30nm and are evenly distributed.

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Abstract

The invention discloses a modified albumin nanoparticle capable of ultrasonically releasing NO gas and a preparation method and application thereof, a part of disulfide bonds in an albumin structure are reduced and oxidized to obtain a group (NO donor structure) capable of ultrasonically releasing NO, and then the modified albumin nanoparticle is prepared by a desolvation method to form a stable nanoparticle. The modified albumin has an SNO group capable of effectively performing ultrasonic excitation to release NO, NO reacts with superoxide anions to form peroxynitrite, albumin functions can be changed, DNA can be damaged, and the modified albumin is helpful to cooperate with chemotherapeutic drugs to kill tumor cells and intracellular pathogens; a desolvation method is used for preparation, toxicity of drugs to normal tissues is avoided, nano particle size distribution is uniform and controllable in the range of 20-500nm, dispersity is good, and large-scale preparation is facilitated.

Description

technical field [0001] The invention belongs to the field of new biomedical materials, and in particular relates to a modified albumin nanoparticle capable of ultrasonically releasing NO signal molecules, a preparation method thereof, and an application in releasing medicine through ultrasonic action. Background technique [0002] Albumin is the most abundant serum protein in the blood. It is often selected as a drug carrier due to its high water solubility, good stability, and high biocompatibility. There are a large number of amino acid residues in the primary structure of albumin, which is Several small molecules (ligands) provide binding sites and are capable of payloads for many different classes of drugs. As the carrier of drug delivery, human serum albumin (HSA) and bovine serum albumin (BSA) are the most studied. HAS is a soluble single-chain globular protein with a molecular weight of 67kDa and composed of 585 amino acids. HAS has many drug binding sites and can bi...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/42A61K41/00A61K45/00A61P35/00A61P31/04B82Y5/00A61K47/54
CPCA61K9/0009A61K41/0033A61K9/5169A61K45/00A61P35/00A61P31/04B82Y5/00A61K47/54
Inventor 杜健军张苇杭时天聪樊江莉彭孝军
Owner DALIAN UNIV OF TECH
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