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A supramolecular hydrogel drug and gene dual carrier material and preparation method thereof

A supramolecular hydrogel and carrier material technology, which is applied in the field of supramolecular hydrogel drug and gene dual carrier materials and its preparation, achieves the effects of mild conditions, convenient and quick preparation method, low concentration and temperature

Active Publication Date: 2019-01-18
佛山市高明绿化纳新材料科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] So far, supramolecular hydrogels and their applications for in situ loading of drugs and genes via host-guest interactions between polymers and cyclodextrins have not been reported.

Method used

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  • A supramolecular hydrogel drug and gene dual carrier material and preparation method thereof
  • A supramolecular hydrogel drug and gene dual carrier material and preparation method thereof
  • A supramolecular hydrogel drug and gene dual carrier material and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] (1) polyethylene glycol-polycaprolactone-dendritic polylysine (mPEG-PCL-G 3 -(G 3 ) 3～8 ) Synthesis of multi-block polymers:

[0042] a. Lysine Lys(boc) protected by double Boc(N,N'-di-tert-butoxycarbonyl) 2 Dissolve in N,N-dimethylformamide, add propargylamine; Boc-protected lysine Lys(boc) 2 The molar ratio of propargylamine to propargylamine is 1:1.2; the system is placed in an ice-water bath and nitrogen protection is passed through at the same time; then 1-hydroxybenzotriazole (HOBt) and benzotriazole-N,N are added to the system ,N',N'-tetramethyluronium hexafluorophosphate (HBTU), the 1-hydroxybenzotriazole (HOBt) and benzotriazole-N,N,N',N'-tetramethyl The ratio of urea hexafluorophosphate (HBTU) was 1:1; after 24 hours at room temperature, the mixed system was diluted with 200 milliliters of ethyl acetate, and then saturated sodium bicarbonate, sodium bisulfate, sodium bicarbonate and Sodium chloride washing; The consumption of described sodium bicarbonate ...

Embodiment 2

[0051] (1) polyethylene glycol-polycaprolactone-dendritic polylysine (mPEG-PCL-G 3 -(G 3 ) 3～8 ) Synthesis of multi-block polymers:

[0052] a. Lysine Lys(boc) protected by double Boc(N,N'-di-tert-butoxycarbonyl) 2 Dissolve in N,N-dimethylformamide, add propargylamine; Boc-protected lysine Lys(boc) 2 The molar ratio of propargylamine to propargylamine is 1:1.2; the system is placed in an ice-water bath and nitrogen protection is passed through at the same time; then 1-hydroxybenzotriazole (HOBt) and benzotriazole-N,N are added to the system ,N',N'-tetramethyluronium hexafluorophosphate (HBTU), the 1-hydroxybenzotriazole (HOBt) and benzotriazole-N,N,N',N'-tetramethyl The ratio of urea hexafluorophosphate (HBTU) was 1:1; after 48 hours at room temperature, the mixed system was diluted with 200 milliliters of ethyl acetate, and then saturated sodium bicarbonate, sodium bisulfate, sodium bicarbonate and Sodium chloride washing; The consumption of described sodium bicarbonate ...

Embodiment 3

[0057] (1) polyethylene glycol-polycaprolactone-dendritic polylysine (mPEG-PCL-G 3 -(G 3 ) 3～8 ) The synthesis of multi-block polymer is the same as in Example 1

[0058] (2) At room temperature at 25°C, the polyethylene glycol-polycaprolactone-dendritic polylysine multi-block polymer A obtained in step (1) was formulated into 1 mL with a mass volume percentage concentration of 10% ( w / v) aqueous solution, under ice-bath conditions, add docetaxel acetone solution with a concentration of 2mg / ml therein, and stir magnetically at 37°C for 36 hours; mPEG-PCL-G 3 -(G 3 ) 3～8 / DTX complex;

[0059] (3) mPEG-PCL-G obtained in step (1) 3 -(G 3) 3～8 Dissolve in pure water to prepare a 1 mg / ml solution, filter and sterilize through a 0.2 μm filter head, mix with the DNA solution according to the N / P value of 2:1-80:1, and let it stand at room temperature for 20 minutes. get mPEG-PCL-G 3 -(G 3 ) 3～8 The polymer / nucleic acid complex solution of / DNA; With mPEG-PCL-G in step (2...

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Abstract

The invention belongs to the field of biomedical materials and discloses a supramolecular hydrogel medicine and gene dual-carrier material and a preparation method thereof. The preparation method comprises the following steps: modifying end groups of a polyethylene glycol-polycaprolactone segmented copolymer, so as to synthetize a segmented copolymer containing cation chain segments; then mixing the polymer with a hydrophobic medicine solution, and further compounding with nucleic acid, thereby obtaining medicine-gene copolymer compound micelle; and further mixing the micelle solution with an alpha-cyclodextrin solution, stirring, and standing at a room temperature so as to obtain the hydrogel. The hydrogel can be used for preparing an injectable medicine gene carrier. The preparation method has the advantages of simplicity in operation, adjustable hydrogel strength and gelating time, molding at room temperature, and no use of chemical cross-linking reaction and organic solvents; the obtained hydrogel has the advantages of temperature sensibility, favorable biocompatibility, obvious transfection and the like, and is expected to be widely applied to the field of biomedical engineering materials.

Description

technical field [0001] The invention belongs to the field of biomedical materials, in particular to a supramolecular hydrogel drug-gene dual carrier material and a preparation method thereof. Background technique [0002] Combination therapy of drugs and genes is a new and effective method for the treatment of cancer and congenital immune system diseases. The key to the implementation of this technology is to select a suitable carrier that can co-load drugs and genes and improve the gene transfection efficiency of the carrier, so that not only the drug can be effectively released in the cell, but the gene can be safely and efficiently in the cell. and stable expression. As a class of biomedical materials that can be used as drug carriers, hydrogels have the characteristics of high loading rate, protection of macromolecular drugs from degradation or removal by organisms, and sustainable release of drug molecules. Research for drug and gene loading and controlled release. F...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/59A61K48/00A61K9/06A61K47/34A61K31/337C08G81/00C08G83/00A61P35/00A61K31/713
CPCA61K9/0019A61K9/06A61K31/337A61K31/713A61K47/34A61K48/0041A61K48/005C08G81/00C08G83/004
Inventor 谭绍早杨雨萌胡家彩
Owner 佛山市高明绿化纳新材料科技有限公司
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