Preparation and application of surface double-modified targeting human serum albumin nano-drug carrier

A technology of human serum albumin and nano-drug carrier, which is applied in the direction of drug combination, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., can solve the problems of lack of active targeting and improve the efficacy of drugs and safety, increase protein water solubility and stability, and improve the effect of plasma half-life

Active Publication Date: 2021-05-04
TIANJIN UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, at present, there is still a lack of stronger active targeting for nano-drugs with HSA as the carrier. More importantly, there is no HSA drug that can target the delivery of drugs to play an anti-tumor effect and inhibit tumor metastasis. carrier

Method used

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  • Preparation and application of surface double-modified targeting human serum albumin nano-drug carrier
  • Preparation and application of surface double-modified targeting human serum albumin nano-drug carrier
  • Preparation and application of surface double-modified targeting human serum albumin nano-drug carrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment example 1

[0047] Synthesis of Intermediate 2

[0048] Take 2 g of polyethylene glycol monomethyl ether with an average molecular weight of 2000 and dissolve it in 14 mL of distilled water, then add 1 mg of 2,2,6,6-tetramethylpiperidine oxide, 0.2 g of potassium bromide, stir in an ice bath, and then add 4.8 8% sodium hypochlorite solution, use 0.5N sodium hydroxide solution to adjust the pH of the system until the pH is stable at about 10, turn to room temperature and stir for 7 hours, add 0.7mL ethanol to annihilate the reaction, adjust the pH to 3 with 4N hydrochloric acid, and use dichloro Extracted with methane, dried over anhydrous sodium sulfate, spin-dried under reduced pressure, recrystallized with ether, and filtered to obtain 1.8 g of white solid.

Embodiment example 2

[0050] Synthesis of compound 8CR-mPEG2000

[0051] Take 0.674g resin octapeptide, add it to 7mL N,N-dimethylformamide, then add 1.9g intermediate 2, 358mg benzotriazole-N,N,N',N'-tetramethylurea hexa Fluorophosphate, 127mg 1-hydroxybenzotriazole, 0.31mL N,N-diisopropylethylamine, reacted at 30°C for 2.5h, detected by ninhydrin reaction method, the resin was colorless, and the reaction was complete. Wash the resin with 10 mL each of N,N-dimethylformamide, isopropanol, and N,N-dimethylformamide for 5 minutes in sequence and drain to obtain Resin-8CR-mPEG2000.

[0052] Preparation of lysate:

[0053] Phenol: ethanedithiol: sulfide anisole: water: trifluoroacetic acid = 5: 5: 2.5: 5: 82.5 (V / V)

[0054] Weigh 0.68g Resin-8CR-mPEG2000, add to 6ml lysate in ice bath, and react at 30°C for 2 hours. The reaction solution was filtered into cold diethyl ether and refrigerated overnight. After centrifugation, the resulting solid was washed three times with ether and dried with argon ...

Embodiment example 3

[0056] Synthesis of compound HSA-SMCC

[0057] Take 3.125mg of 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid sulfosuccinimide sodium salt, add 0.25mL of distilled water, stir at a temperature of about 40°C It was dissolved, and then 1.125 mL of PBS buffer solution was added, which was added to 8.94 mL of PBS buffer solution containing 20 mg of human serum albumin, protected by argon, and stirred at room temperature for 5 h. Dialyze in distilled water for 24 hours with a dialysis bag with a molecular weight cut-off of 8000-14000, and freeze-dry to obtain 20 mg of a white solid.

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Abstract

The invention provides the preparation and application of a surface double-modified human serum albumin as a tumor-targeting nano-drug carrier. The targeted nano-drug carrier includes human serum albumin, polyethylene glycol and E-selectin peptide ligands . The targeted nano drug carrier is formed by coupling the E-selectin peptide ligand and polyethylene glycol to the HSA surface by using the thioether formed by the activated HSA and the sulfhydryl group of the E-selectin peptide ligand as a connecting bridge. The targeted nano-drug carrier can be loaded with hydrophobic anti-tumor drugs and processed to form nanoparticles with a certain particle size, which not only increases the solubility and stability of hydrophobic anti-tumor drugs, but also E-selectin peptide ligands can actively recognize The highly expressed E-selectin on endothelial cells is activated at the tumor site and combined with it, thereby competitively inhibiting the combination of tumor cells and E-selectin to achieve the purpose of inhibiting tumor cell adhesion and migration.

Description

technical field [0001] The present invention relates to the technical field of nano-medicine, and more specifically, to a targeted nano-medicine carrier and its preparation method and application. [0002] technical background [0003] HSA is the protein with the highest content in plasma. It has a long half-life in vivo. Its three-dimensional structure is heart-shaped and contains multiple ligand binding sites. It is a natural carrier for hydrophobic substances in vivo. organize. HSA is relatively stable in nature and has a certain degree of tolerance to acid-base environments, temperatures, and organic solvents, so it is suitable for the preparation of various nanoparticles. The surface of human serum albumin contains many functional groups such as carboxyl and amino groups, which can be used to modify the surface of serum albumin nanoparticles through covalent bonds, surface coating or electrostatic adsorption with various groups. The modified serum albumin nano-drug car...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K47/42A61K47/10A61K47/64A61K47/60A61K31/337A61K31/704A61P35/00A61P35/04
CPCA61K9/146A61K31/337A61K31/704A61K47/60A61K47/64A61K47/643A61P35/00A61P35/04
Inventor 郭娜郁彭李凤燕汤晶晶郝甜甜付颖王浩猛滕玉鸥王栋
Owner TIANJIN UNIV OF SCI & TECH
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