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Ultrasonic activateable medicine-release albumin nanoparticles as well as preparation method and application thereof

A nanoparticle and albumin technology, applied in the field of biomedical new materials, can solve the problems of drug release rate of less than 20%, uncontrollable rapid drug release, and low drug release, so as to avoid toxicity and facilitate large-scale preparation , good dispersion effect

Inactive Publication Date: 2020-07-14
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This kind of albumin drug nanoparticles is relatively stable under normal physiological conditions, and the drug release rate is less than 20%. It has a sustained drug release effect under acidic or reducing conditions, but it cannot achieve rapid and reliable drug release under physiological conditions. controlled release
[0006] In short, the existing technology has the problem that albumin nanoparticles cannot control the rapid release of drugs under physiological conditions, and can only release drugs slowly under endogenous stimuli such as acidity or reduction. At the same time, the traditional light-controlled release has tissue penetration. Defects such as poor drug release due to poor performance need to be solved urgently

Method used

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  • Ultrasonic activateable medicine-release albumin nanoparticles as well as preparation method and application thereof
  • Ultrasonic activateable medicine-release albumin nanoparticles as well as preparation method and application thereof
  • Ultrasonic activateable medicine-release albumin nanoparticles as well as preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0050] Preparation of Molecular Active Ester of Chemical Crosslinker

[0051] Weigh 50 mg of 4,4'-azobis(4-cyanovaleric acid) into a 25 mL flask, add 2 mL of anhydrous dimethyl sulfoxide to it, and magnetically stir until completely dissolved. Under stirring conditions, 50 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 80 mg of N-hydroxysuccinimide were successively added until completely dissolved. After reacting for two hours at 37°C, a colorless and clear 4,4'-azobis(4-cyanovaleric acid) active ester solution was obtained.

Embodiment 2

[0053] Preparation of albumin nanoparticles activated by ultrasound

[0054] Bovine serum albumin-based nanoparticles (BSA-ACVA) were prepared by a desolvation-chemical cross-linking method. In principle, weigh 90 mg of bovine serum albumin powder and dissolve in 3 mL of ultrapure water. Add 0.1mol / L sodium hydroxide aqueous solution dropwise, adjust the pH value of the solution to 9.0, continue stirring for one hour, add 6mL absolute ethanol dropwise at a constant speed of 4mL / min, after the desolvation process is completed, then slowly add 80 μL of the linker solution was cross-linked and solidified, and the reaction was continued overnight at 37°C in the dark to obtain a stable albumin nanoparticle solution. Rotate the obtained albumin nanosuspension at 37°C to remove ethanol, centrifuge at 12000rpm, wash the precipitate with deionized water, remove uncrosslinked albumin and excess crosslinking agent with deionized water, repeat three times, Finally, disperse with a certa...

Embodiment 3

[0057] Preparation of Ultrasound-Activatable Drug Albumin Nanoparticles

[0058] Drug-loaded bovine serum albumin nanoparticles (BSA-ACVA-DOX) were prepared by desolvation-chemical cross-linking method. Weigh 90 mg of bovine serum albumin powder and dissolve it in 3 mL of ultrapure water, add 6.0 mg of doxorubicin hydrochloride powder, and stir until completely dissolved. Add 0.1mol / L sodium hydroxide aqueous solution dropwise, adjust the pH value of the solution to 9.0, continue stirring for one hour, add 6mL absolute ethanol dropwise at a constant speed of 4mL / min, after the desolvation process is completed, then slowly add 80 μL of the linker solution was cross-linked and solidified, and the reaction was continued overnight at 37°C in the dark to obtain a stable albumin nanoparticle solution. Rotate the obtained albumin nanosuspension at 37°C to remove ethanol, centrifuge at 12000rpm, wash the precipitate with deionized water, remove uncrosslinked albumin and excess crossl...

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Abstract

The invention discloses ultrasonic activateable medicine-release albumin nanoparticles as well as a preparation method and application thereof. The ultrasonic activateable medicine-release albumin nanoparticles adopt azo-group-containing small molecules as a chemical cross-linking agent and albumin as a nanoparticle framework, coats an anti-cancer medicine and is prepared by using a solvent removing method; and the nanoparticles have particle sizes of 50-300nm under normal physiological conditions, and are uniform and stable in distribution. Under the action of ultrasonic waves acceptable by aliving body, the azo bond of the cross-linking agent can be broken, then the structure of the albumin nanoparticles can be damaged, medicines coated by the albumin nanoparticles can be rapidly released, the release amount of the medicines can be regulated and controlled through ultrasonic time and intensities, and the maximum release amount is up to 70%. Through intensive permeability of the ultrasonic waves, the albumin nanoparticles are capable of achieving rapid and controlled release of medicines at tumor tissue.

Description

technical field [0001] The invention belongs to the field of biomedical new materials, and in particular relates to an albumin drug nanoparticle that can be activated by ultrasound for drug release, a preparation method thereof, and an application of the drug release through ultrasound. 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. Small molecules (ligands) provide binding sites that allow for payloads of 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 bind to salicylic acid, warfarin, diazepam, penicillin, and penicillin. BSA is a globular heart-shaped protein with a molecular ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/42A61K41/00A61K45/00A61P35/00B82Y5/00
CPCA61K9/0009A61K9/5169A61K41/0033A61K45/00A61P35/00B82Y5/00
Inventor 杜健军张宇时天聪樊江莉彭孝军
Owner DALIAN UNIV OF TECH
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