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Preparation method of copper-free click crosslinking polysaccharide microspheres

A polysaccharide and microsphere technology, used in the preparation of microspheres, microcapsule preparations, etc., can solve the problems of loss of sustained release ability of microspheres, poor stability of polysaccharide microspheres, protein denaturation, etc., to ensure cell compatibility. safety, low cost of raw materials, and low cross-linking temperature

Inactive Publication Date: 2016-11-23
NANJING UNIV OF SCI & TECH
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0009] (1) The microspheres containing sodium alginate are mostly ionically cross-linked with calcium chloride, and the physical cross-linked polysaccharide microspheres have poor stability
Under physiological conditions, calcium ions will inevitably be replaced with other divalent ions, which makes the microspheres easily dissolve and lose the ability of sustained release
[0010] (2) The prepared polysaccharide microspheres or hydrogels are mostly cross-linked with chemical reagents such as glutaraldehyde or cuprous ions. These chemical cross-linking agents are cytotoxic, and the cross-linking process leads to protein denaturation, and the toxic residue It will have toxic and side effects on the human body, making it difficult for clinical use

Method used

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  • Preparation method of copper-free click crosslinking polysaccharide microspheres
  • Preparation method of copper-free click crosslinking polysaccharide microspheres
  • Preparation method of copper-free click crosslinking polysaccharide microspheres

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preparation example Construction

[0033] The preparation method of copper-free click-crosslinked polysaccharide microspheres of the present invention uses chitosan and sodium alginate as matrix materials, and is formed by biocompatible click-crosslinking, specifically comprising the following steps:

[0034] Step 1, dissolving chitosan and 1-hydroxybenzotriazole in water at room temperature, the chitosan and 1-hydroxybenzotriazole are in an equal mass ratio, and the mass concentrations of both are 0.05 to 0.15% ;

[0035] Step 2. Dissolve cyclooctyne-3-glycolic acid in a mixed solvent of tetrahydrofuran / water at room temperature, the volume ratio of tetrahydrofuran to water in the mixed solvent of tetrahydrofuran / water is 1:3, cyclooctyne-3 - the mass concentration of glycolic acid is 0.5-1%;

[0036] Step 3. At room temperature, mix the two solutions obtained in step 1 and step 2 according to the volume ratio of 1:1, then add diisopropylethylamine, the mass concentration of diisopropylethylamine is 0.05-0.2%...

Embodiment 1

[0049] The specific operation steps are:

[0050] (1) 0.05 gram of chitosan and 0.05 gram of 1-hydroxybenzotriazole are dissolved in 100 milliliters of water at room temperature;

[0051] (2) Dissolve 0.5 g of cyclooctyne-3-glycolic acid in a mixed solvent of 100 ml of tetrahydrofuran / water (volume ratio 1:3) at room temperature;

[0052] (3) Fully mix the two solutions obtained in (1) and (2) at room temperature, add 0.1 g of diisopropylethylamine, stir and react at 0°C for 10 hours, dialyze for 2 days and freeze-dry to obtain cyclooctyne Chitosan (structural schematic diagram see figure 1 );

[0053] (4) Dissolve 0.2 g of sodium alginate and 0.2 g of water-soluble carbodiimide in 100 ml of water at room temperature, then add 0.2 ml of 11-azido-3,6,9-triethylether-1-amine, and stir at room temperature Reacted for 22 hours, lyophilized after 2 days of dialysis to obtain sodium azide alginate (see figure 1 );

[0054] (5) Prepare respectively cyclooctynylated chitosan aque...

Embodiment 2

[0060] The specific operation steps are:

[0061] (1) 0.08 gram of chitosan and 0.08 gram of 1-hydroxybenzotriazole are dissolved in 100 milliliters of water at room temperature;

[0062] (2) Dissolve 0.6 g of cyclooctyne-3-glycolic acid in a mixed solvent of 100 ml of tetrahydrofuran / water (volume ratio 1:3) at room temperature;

[0063] (3) Fully mix the two solutions obtained in (1) and (2) at room temperature, add 0.15 g of diisopropylethylamine, stir and react at 0°C for 11 hours, dialyze for 2 days and freeze-dry to obtain cyclooctyne Chitosan;

[0064] (4) Dissolve 0.2 g of sodium alginate and 0.5 g of water-soluble carbodiimide in 100 ml of water at room temperature, then add 0.35 ml of 11-azido-3,6,9-triethylether-1-amine, and stir at room temperature React for 23 hours, lyophilize after 2 days of dialysis to obtain sodium alginate azide;

[0065] (5) Prepare respectively cyclooctynylated chitosan aqueous solution and azide sodium alginate aqueous solution with a m...

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Abstract

The invention discloses a preparation method of copper-free click crosslinking polysaccharide microspheres. The preparation method comprises the following steps that chitosan and 1-hydroxyl benzotriazole are dissolved in water at room temperature, and cyclooctyne-3-glycolic acid is dissolved in a tetrahydrofuran / water mixed solvent; after the two solutions are mixed, diisopropylethylamine is added, stirring reaction is performed, and cyclooctyne chitosan is obtained through dialysis and freeze-drying; sodium alginate and carbodiimide are dissolved in water, 11-azido-3,6,9-triethyl ether-1-amine is added, stirring reaction is performed, and azido sodium alginate is obtained through dialysis and freeze-drying; water solutions of the cyclooctyne chitosan and the azido sodium alginate are respectively prepared, after mixing according to the volume ratio, emulsifier Span-80 containing paraffin oil is added, and an emulsification emulsion is obtained through ultrasonic emulsification; the emulsification emulsion volatilizes and stays overnight and is poured into isopropanol for precipitation of microspheres, and the crosslinking polysaccharide microspheres are obtained through freeze-drying after cleaning. The process is simple, makes products safe and non-toxic and is suitable for the medical fields of drug release, gene therapy, tissue engineering and the like.

Description

technical field [0001] The invention belongs to the technical field of preparation of biological materials, in particular to a method for preparing copper-free click-crosslinked polysaccharide microspheres. Background technique [0002] Microsphere materials with biodegradable properties can be used for the embedding and release of drugs, proteins or genes, and have been widely used in research in the fields of drug controlled release, tissue engineering and regenerative medicine. Selecting the appropriate microsphere system can realize the slow release of the drug in the body and achieve the ideal therapeutic effect. Natural polymers have excellent biocompatibility and tunable biodegradability, and are ideal matrix materials for preparing microspheres. Commonly used polysaccharides include: chitosan, sodium alginate, hyaluronic acid, cellulose, and heparin. Among them, chitosan and alginic acid are ideal materials for preparing cells and drug carriers. On the one hand, th...

Claims

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Application Information

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IPC IPC(8): B01J13/14C08G81/00C08B37/08C08B37/04
Inventor 谈华平陈会男范茗缪羽婷毛嘉慧张紫薇
Owner NANJING UNIV OF SCI & TECH
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