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A kind of temperature, redox sensitive drug delivery material linked by diselenide bond and its preparation and application

A drug and diselenide technology, applied in the field of biomedical materials and tumor treatment, can solve the problems of drug leakage, discount of cancer treatment effect, wide molecular weight distribution, etc., to achieve good biocompatibility and stability, significant tumor treatment effect, The effect of narrow molecular weight distribution

Active Publication Date: 2020-07-28
SHAANXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] At present, clinical anticancer drugs have greatly reduced the therapeutic effect of cancer due to defects such as poor stability, poor water solubility, and bioheterogeneous dispersion. in the kernel of the bundle
However, after the drug-loaded micelles are diluted by body fluids during the systemic circulation, the original micellar structure is destroyed, leading to early leakage of the drug, which has great side effects on normal tissues.
In addition, slow response to physiological signals specific to cancerous sites, poor stability of drug carriers, and unsatisfactory biocompatibility are important factors that limit the use of drug carriers
Previously, the selenium-containing drug delivery materials reported in the literature were difficult to prepare, poor in water solubility, difficult to modify, and wide in molecular weight distribution, so it was quite difficult to introduce them into drug delivery materials

Method used

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  • A kind of temperature, redox sensitive drug delivery material linked by diselenide bond and its preparation and application
  • A kind of temperature, redox sensitive drug delivery material linked by diselenide bond and its preparation and application
  • A kind of temperature, redox sensitive drug delivery material linked by diselenide bond and its preparation and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 1. Preparation of diselenodipropionate-polyethylene glycol ester

[0040]0.304g (1mmol) of 3,3'-diselenodipropionic acid shown in formula I (according to literature "Cheng, G.; He, Y.; Xie, L.; Nie, Y.; He, B. ; Zhang, Z.; Gu, Z.Development of a reduction-sensitivediselenide-conjugated oligoethyleneimine nanopaticulate system as a genecarrier.International Journal of Nanomedicine, 2012,7,3991-4006" prepared by the method disclosed), 2g (1mmol) Polyethylene glycol 2000, 0.122g (1mmol) 4-dimethylaminopyridine dissolved in 10mL dichloromethane and N,N-dimethylformamide mixed solvent (V 二氯甲烷 / V N,N-二甲基甲酰胺 =1 / 1), activated in an ice bath for 3 hours; 0.4123g (2mmol) N,N-dicyclohexylcarbodiimide was dissolved in 4mL of dichloromethane, and the solution was dropped into the reaction system, under nitrogen The reaction was carried out at room temperature under atmosphere for 24 hours. After the reaction was completed, the insoluble matter was removed by filtration, and the f...

Embodiment 2

[0049] 1. Preparation of diselenodipropionate-polyethylene glycol ester

[0050] This step only needs to replace polyethylene glycol 2000 in Step 1 of Example 1 with Polyethylene Glycol 4000, and the other steps are the same as Step 1 of Example 1 to obtain diselenodipropionic acid-polyethylene glycol shown in formula II-2. Ethylene glycol ester, productive rate 73%, its weight-average molecular weight is M w =47922g mol -1 , number average molecular weight M n =29655g mol -1 , polydispersity index = 1.616.

[0051]

[0052] 2. Preparation of macromolecular initiator

[0053] In this step, the diselenodipropionic acid-polyethylene glycol ester shown in the equimolar formula II-2 is used to replace the diselenodipropionic acid-polyethylene glycol ester shown in the formula II-1 in Step 2 of Example 1, Other steps were the same as Step 2 of Example 1 to obtain the macroinitiator represented by formula III-2 with a yield of 43.3%.

[0054]

[0055] 3. Preparation of d...

Embodiment 3

[0059] Step 1 and Step 2 of this embodiment are the same as those of Embodiment 2. In step 3, the amount of N-isopropylacrylamide is doubled, and the other steps are the same as in step 3 of Example 2 to obtain diselenodipropionic acid-polyethylene glycol ester- b-Poly(N-isopropylacrylamide) copolymer, a temperature, redox-sensitive drug delivery material linked by diselenide bonds, with a yield of 33.3%.

[0060]

[0061] Such as figure 1 Shown, HOCH 2 CH 2 S– and HO CH 2 CH 2 The methylene chemical shifts in S- are at 2.75 and 3.12, 3.29ppm, respectively, 1.14, 4.01, 6.46, 1.36, and 1.73ppm are characteristic peaks in poly(N-isopropylacrylamide), and 3.67, 4.27ppm are poly(N-isopropylacrylamide). The characteristic peaks of ethylene glycol, the above-mentioned characteristic peaks prove that the temperature and redox-sensitive drug delivery materials connected by diselenide bonds were successfully synthesized.

[0062] Such as figure 2 Shown, 526 and 840cm -1...

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Abstract

The invention discloses a temperature and redox-sensitive type drug delivery material connected by diselenide bonds and preparation and application thereof. The temperature and redox-sensitive type drug delivery material is a diseleno dipropionic acid-polyethylene glycol ester-b-poly(N-isopropylacrylamide) copolymer, and is specifically prepared by the following steps of enabling the structure containing a plurality of diselenide bonds after esterification of diseleno dipropionic acid and polyethylene glycol to react with 2-bromoisobutyryl bromide, so as to obtain a macromolecular initiator; initiating the N-isopropylacrylamide to generate atom transfer and free radical polymerizing. The temperature and redox-sensitive type drug delivery material has the advantages that the preparation issimple and convenient, and the conditions are mild; the material is assembled by self into micelles in a water solution, the diselenide bonds and the poly(N-isopropylacrylamide) in the structure can be respectively used for performing sensitivity response on high-concentration oxidative and reductive matter and higher temperature in cancer lesion tissues, and the problems of difficulty in carriersynthesis, poor water solubility, difficulty in modifying and the like in the selenium-containing drug are solved; the biocompatibility is good, the good effect is obtained in the tumor inhibiting test, and the temperature and redox-sensitive type drug delivery material can be used as a drug transfer material to be applied into the cancer targeted therapy.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a temperature- and redox-sensitive drug delivery material connected by a diselenide bond and a preparation method thereof. The material has multiple temperature, redox response sites and stability, It has good biocompatibility and can be used in the field of tumor treatment. Background technique [0002] At present, clinical anticancer drugs have greatly reduced the therapeutic effect of cancer due to defects such as poor stability, poor water solubility, and bioheterogeneous dispersion. in the core of the bundle. However, after the drug-loaded micelles are diluted by body fluids during the systemic circulation, the original micellar structure is destroyed, leading to early leakage of the drug, which has great side effects on normal tissues. In addition, slow response to physiological signals specific to cancerous sites, poor stability of drug carriers,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08F283/06C08F220/54C08G65/337A61K9/107A61K31/337A61K47/34A61P35/00
CPCA61K9/1075A61K31/337A61K47/34A61P35/00C08F283/06C08G65/337C08F220/54
Inventor 徐峰徐静文罗延龄
Owner SHAANXI NORMAL UNIV