Ph-responsive nanometer drug delivery system based on dendrimers modified by short-chain alkane and preparation method and application of drug delivery system

A nano-drug delivery system and dendrimer technology, applied in the field of nano-drug delivery system, can solve the problems of cell tissue damage, uncontrollable release process, etc.

Inactive Publication Date: 2016-07-13
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because the whole release process is uncontrollable, it may cause certain damage to normal cells and tissues

Method used

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  • Ph-responsive nanometer drug delivery system based on dendrimers modified by short-chain alkane and preparation method and application of drug delivery system
  • Ph-responsive nanometer drug delivery system based on dendrimers modified by short-chain alkane and preparation method and application of drug delivery system
  • Ph-responsive nanometer drug delivery system based on dendrimers modified by short-chain alkane and preparation method and application of drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Add H-Lys-OMe·2HCl (2.5g), Boc-L-Lys(Boc)-OH (12.81g), EDC?HCl (7.0g) and HOBT (5.0g) into the reaction flask and redistill with 80ml dissolved in dichloromethane, under the protection of nitrogen, add DIPEA10.2ml, react at room temperature for 48h, rotary steam, add chloroform to dilute, and then use saturated NaHCO 3 solution, washed with HCl (1M) and saturated NaCl solution, anhydrous MgSO 4 After drying overnight, the product 2 (MeO-D-Boc) was obtained by column separation.

[0051] Second-generation lysine dendrimers (MeO-D):

[0052] Under nitrogen protection, MeO-D-Boc (1.82 g, 2 mmol) was dissolved in 6 ml CH 2 Cl 2 , then added TFA7ml, reacted at room temperature for 7h, rotary steamed, diethyl ether precipitated, removed diethyl ether to obtain a white powder (MeO-D).

[0053] Short-chain alkane-modified second-generation lysine dendrimers (MeO-DH):

[0054] Under the protection of nitrogen, dissolve MeO-D (2.4mmol) in 30ml of anhydrous methanol, add exce...

Embodiment 2

[0060] Example 3: Preparation of amphiphilic compound (HA-DH)

[0061] The hydrazide group of Hydrazine-DH reacts with the aldehyde group of the hyaluronic acid derivative. Under the protection of nitrogen, the Hydrazine-DH and HA-CHO obtained in the above reaction were dissolved in the buffer solution of pH 7.4 at the same ratio, and reacted at 40° C. for 24 hours. After the reaction was completed, it was dialyzed in water and freeze-dried to obtain the product (HA-DH).

Embodiment 3

[0062] Embodiment 4: the critical self-assembly concentration of HA-DH

[0063] Using pyrene as a fluorescent probe, the critical self-assembly concentration of HA-DH was investigated by fluorescence spectroscopy. First dilute the solution of pyrene in acetone to 1.2*10 -6 M, take 1ml and add it to a 10ml glass bottle, put it in a vacuum drying oven to remove acetone, then add 2ml of materials with different concentrations, heat at 60°C for 1h, cool at room temperature and place in a dark place overnight. Taking 390nm as the emission, scanning the excitation spectrum of 300-360nm, the critical micelle concentration was obtained by the function of the ratio of I338 / I334 in the fluorescence spectrum of pyrene and logC.

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Abstract

The invention discloses a nanometer drug delivery system which is self-assembled on the basis of grafting dendrimers modified by short-chain alkane to natural polysaccharide and has a pH-responsive performance, belonging to the field of biomedical materials. The drug delivery system comprises aldehydated hydrophilic natural polysaccharide, dendrimers modified by short-chain alkane, an antitumor drug and a targeting ligand for specific tumor identification; the natural polysaccharide and the dendrimers modified by short-chain alkane are formed into a amphiphilic compound through hydrazone bonds; a hydrophobic drug is wrapped inside a cavity of a self-assembled body by means of the hydrophilicity and the hydrophobicity; the targeting ligand for specific tumor identification and drug-loaded nanoparticles are physically mixed to promote the delivery of the drug in tumor tissues and cells. The nanometer delivery system having the pH-responsive performance can realize active targeting and passive targeting, is beneficial for accumulation of the drug in a tumor site, and can make an intelligent response to a slightly acid environment of lysosome/endosome in the tumor cells, thus releasing the drug and realizing the delivery of the drug in the tumor cells, and therefore, the nanometer delivery system is a multifunctional tumor targeted drug delivery system.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a nano drug delivery system responsive to tumor microenvironment. technical background [0002] At present, most of the antineoplastic drugs widely used in clinical practice are non-selective drugs. After entering the body, these anticancer drugs quickly reach a high drug concentration in the blood and are quickly metabolized from the body. There are relatively large toxic and side effects, and the therapeutic efficiency of the medicine is reduced simultaneously. In order to improve the curative effect and reduce the side effects of drugs, a safe and non-toxic intelligent drug delivery system has emerged. [0003] As a drug carrier, polymer micelles have better stability than small molecule micelles. It can increase the solubility of insoluble drugs, make the drugs target the tumor site and release them slowly, reduce adverse reactions, and improve the bioavailab...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/36A61K31/704A61P35/00
CPCA61K9/5161A61K31/704
Inventor 顾忠伟何一燕马胜男周洁姜倩岳冬
Owner SICHUAN UNIV
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