PH-responsive, folic acid-targeting and ursolic acid-supporting silica-chitosan-folic acid nano material and application

A silicon dioxide and folic acid targeting technology, applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, organic active ingredients, etc., can solve problems such as low bioavailability and poor water solubility of ursolic acid , achieve good biocompatibility, solve low bioavailability, and increase targeting effect

Inactive Publication Date: 2016-08-17
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The prepared nanomedicine not only solves the shortcomings of poor water solubility and low bioavailability of ursolic acid, but also selectively concentrates on tumor cells by using folic acid and folic acid receptors on the surface of tumor cells; and then tumor cells undergo endocytosis Uptake of the nano-drug; finally, according to the characteristics of the acidic microenvironment of tumor cell growth, the drug can be selectively targeted and released to improve the anti-tumor effect and reduce the side effects of the drug

Method used

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  • PH-responsive, folic acid-targeting and ursolic acid-supporting silica-chitosan-folic acid nano material and application
  • PH-responsive, folic acid-targeting and ursolic acid-supporting silica-chitosan-folic acid nano material and application
  • PH-responsive, folic acid-targeting and ursolic acid-supporting silica-chitosan-folic acid nano material and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Preparation of carboxylated mesoporous silica:

[0029] (1) Weigh 0.6 g of cetyltrimethylammonium bromide (CTAB), dissolve in 90 mL of ultrapure water, add 10 mL of ethylene glycol (EG), and 2.75 mL of ammonia water (25%~28%). The above solution was stirred at 60°C for 30 min, then 1.0 mL of tetraethoxysilane (TEOS) and 0.2 mL of 2-cyanoethyltriethoxysilane (CPTES) were added rapidly, and the reaction was stirred in a constant temperature water bath at 60°C for 2 h. Aging at a constant temperature for 24 h to obtain a milky white suspension;

[0030] (2) Centrifuge the milky white suspension obtained in the above (1) at 13000rpm for 30min, wash and centrifuge repeatedly with water and ethanol, then disperse in acidic ethanol (concentrated hydrochloric acid: ethanol = 5:1, V:V) and heat Reflux for 24 hours, centrifuge after the end of the reflux to remove unreacted template agent CTAB, freeze-dry;

[0031] (3) The reaction product obtained in the above (2) wa...

Embodiment 2

[0032] Embodiment 2 Preparation of chitosan and folic acid conjugate CS-FA:

[0033] (1) Preparation of folic acid active ester: Weigh 100 mg of folic acid (FA), dissolve it in 10 mL of dimethyl sulfoxide (DMSO), add 50 mg of EDC, and stir for 1 h at room temperature in the dark to obtain reddish-brown folic acid active ester. Esters in DMSO;

[0034] (2) Preparation of folic acid-coupled chitosan: Weigh 40mg of chitosan (CS) and dissolve it in 20mL of 1% acetic acid solution, slowly add the DMSO of folic acid active ester obtained in the above step (1) under magnetic stirring conditions The solution was reacted at room temperature in the dark for 16 h, then the pH was adjusted to neutral with 1M NaOH, centrifuged at 13,000 rpm for 30 min, washed with ultrapure water and centrifuged three times, and freeze-dried to obtain CS-FA.

Embodiment 3

[0035] Example 3 Preparation of chitosan-coated mesoporous silica

[0036] Weigh 30mg carboxylated mesoporous silica (MSN-COOH), dissolve in 30mL N-N dimethylformamide (DMF), add 100mg 1-(3-dimethylaminopropyl)-3-ethylcarbodi imine hydrochloride (EDC) and 50mg N-hydroxysuccinimide (NHS), stirred at room temperature for 4 hours; then added 5mL 2% (w / w) chitosan solution (2% (w / w ) acetic acid as a solvent), stirred at room temperature for 12 hours, centrifuged at 13,000 rpm for 30 min, washed with ultrapure water and centrifuged three times, and freeze-dried to obtain MSN-CS. And the sample was tested for particle size, the results are shown in Figure 4 , the average particle size is 190nm;

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Abstract

The invention relates to pH-responsive, folic acid-targeting and ursolic acid-supporting silica-chitosan-folic acid nano material and application. First, an antitumor drug, ursolic acid, is supported to inner ducts of carboxylic mesoporous silica; second, d partial amino groups in tumor cell-targeting molecules, folic acid and chitosan, are linked through amido bonds to prepare a conjugate; third, the conjugate is conjugated with drug-supporting carboxylic mesoporous silica through amido bonds to obtain the material. The nano support material prepared herein has uniform particle size distribution, good dispersity, large specific surface area and good biocompatibility; the defect that the ursolic acid is poor in water solubility and low in bioavailability can be solved; the release of ursolic acid can be sustained, and the release of the ursolic acid at low pH is significantly higher than that in neutral condition; this material has specific targeting for folate receptor high-expressed tumor cells, antitumor effect of ursolic acid can be further improved, and toxic and side effect upon normal tissue cells can also be reduced.

Description

technical field [0001] The invention relates to a mesoporous silicon dioxide-chitosan-folic acid nanometer material with pH responsiveness and folic acid targeting and loaded with ursolic acid and its application. Background technique [0002] Ursolic acid (UA) is a pentacyclic triterpenoid compound derived from a variety of natural plants in nature. In particular, its remarkable anticancer activity has attracted the attention of researchers at home and abroad, showing great clinical application potential and good application prospects. Although ursolic acid is being paid more and more attention to by researchers in the field of pharmacy because of its high efficiency and low toxicity, the clinical development and application of ursolic acid as an anticancer drug at home and abroad is very limited. The reasons are as follows: 1) The solubility of ursolic acid itself in water is small, resulting in low bioavailability, which greatly weakens the effect of its in vivo experime...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K31/56A61K47/04A61K47/36A61K47/22A61P35/00
CPCA61K31/56
Inventor 邵敬伟迟婷李涛沈艺玲
Owner FUZHOU UNIV
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