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Method for preparing folic acid coupling hydroxypropyl chitosan nano particles

A folic acid-coupled hydroxypropyl chitosan and folic acid-coupled hydroxypropyl shell technology, which is applied in the field of preparation of folic acid-coupled hydroxypropyl chitosan nanoparticles, can solve problems such as toxic effects and abnormal metabolism, Achieve the effects of controllable particle size, simple production process and mild reaction conditions

Inactive Publication Date: 2008-08-06
STATE GRID CORP OF CHINA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Organic solvents cannot be metabolized normally in the human body and have certain toxic effects

Method used

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  • Method for preparing folic acid coupling hydroxypropyl chitosan nano particles

Examples

Experimental program
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Effect test

Embodiment 1

[0011] The invention uses chitosan with a degree of deacetylation greater than 90% as a raw material, reacts it with excess propylene oxide under alkaline conditions to generate water-soluble hydroxypropyl chitosan. Prepare hydroxypropyl chitosan into an aqueous solution with a concentration of 2.0mg / ml, filter it with 0.22μm filter paper, add an equal volume of 120μg / ml folic acid solution, heat to 70°C under continuous stirring, and react in the dark for 70 minutes, the product Cool to room temperature and perform dialysis for 24 hours. During the dialysis process, take the dialysate every 2 hours, measure the content of free folic acid on an ultraviolet spectrophotometer, monitor the dialysis effect, and freeze-dry the product after dialysis to obtain light yellow folic acid-coupled hydroxypropyl Chitosan. Measure 5ml of 1.0mg / ml folic acid-coupled hydroxypropyl chitosan aqueous solution in a three-necked flask, adjust the pH between 5-6, and slowly add 0.8mg / ml polyphospho...

Embodiment 2

[0014] The preparation of folic acid-coupled hydroxypropyl chitosan is the same as in Example 1. Measure 5ml of 2.0mg / ml folic acid-coupled hydroxypropyl chitosan aqueous solution in a three-necked flask, adjust the pH between 5-6, and slowly add 0.8mg / ml polyphosphoric acid dropwise under continuous magnetic stirring conditions For sodium solution, the dropping rate is 20-40 drops / min, and the dropping is stopped when the yellow color of the solution fades and opalescence appears slightly.

[0015] It can be seen from the transmission electron microscope photo in Fig. 2 that the folic acid-coupled hydroxypropyl chitosan nanoparticles present a relatively regular spherical shape, and the particle size is about 360nm. The particle size in Example 2 is larger than that in Example 1, which is mainly due to the increase in the concentration of the reactant folic acid-coupled hydroxypropyl chitosan.

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Abstract

The invention relates to a folic acid coupling hydroxypropyl chitose nanometer particle and a corresponding preparation method, wherein the preparation method comprises mixing hydroxypropyl chitose water solution with folic acid in same volume, reacting completely at 70 DEG C without light, dialyzing for 24h, freezing and drying dialyzed product to obtain folic acid coupling hydroxypropyl chitose light yellow solid, adjusting the pH value of folic acid coupling hydroxypropyl chitose water solution to 5-6, adding sodium polyphosphate solution until the light yellow fades and appears opalescence, to obtain nanometer particle. The prepared folic acid coupling hydroxypropyl chitose nanometer particle has significant targeting effect on tumor cell, controllable particle diameter, biological degradation, non toxicity and mild process, thus is suitable for target slow-release carrier of protein drug.

Description

technical field [0001] The invention relates to a preparation method of folic acid-coupled hydroxypropyl chitosan nanoparticle, which has obvious targeting effect on tumor cells, has controllable particle size and good stability, and can be used as a targeting drug carrier. Background technique [0002] Antitumor drugs often have low selectivity, and may kill normal cells in the body while killing tumor cells, resulting in relatively large toxic and side effects. Folate receptor is a specific target for tumor selective drug delivery, and its activity and quantity on the membrane surface of various tumor cells (such as ovarian cancer, colorectal cancer, lung cancer, renal cell carcinoma, etc.) are significantly higher than that of normal cells. Since the combination of receptors and their ligands has the characteristics of specificity, selectivity, and strong affinity, the use of ligands as drug carriers or coupling with carriers can increase the concentration of drugs in the...

Claims

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Application Information

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IPC IPC(8): C08B37/08A61K47/48A61P35/00A61K47/36
Inventor 谢宇尚晓娴
Owner STATE GRID CORP OF CHINA
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