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Preparation method of doxorubicin nanoparticles with folate-modified chitosan as carrier

A nanoparticle and doxorubicin technology, which is applied in the field of preparation of doxorubicin nanoparticles, can solve the problems of lack of targeting, low gene transfection efficiency and unsatisfactory results in gene therapy, and achieve active targeting. properties, enhanced encapsulation efficiency and stability, and the effect of easy storage

Pending Publication Date: 2019-12-17
ZHEJIANG SCI-TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Although gene therapy has made a lot of achievements in basic research, the results of clinical trials are not satisfactory. The main problems are low gene transfection efficiency, poor vector safety and lack of targeting in gene therapy.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] 1) dissolving doxorubicin in water to obtain a doxorubicin solution with a concentration of 4 wt %; dissolving polydopamine in water to obtain a polydopamine solution with a concentration of 2 wt %; precooling the solution for subsequent use;

[0037] 2) Weigh 1g of folic acid and place it in a container, dissolve it in anhydrous DMSO, then add 0.67g of EDC and 0.4g of NHS, stir in a dark room at room temperature for 1 hour to fully dissolve the folic acid;

[0038] 3) Obtained the DMSO solution of folic acid active ester, and the solution is wine red;

[0039] 4) Weigh 1g of chitosan powder, dissolve in 1.5% acetic acid solution, mix evenly, and adjust pH=5.5, obtain chitosan solution after ultrasonic;

[0040] 5) In a dark room, slowly add the chitosan solution to 40 mL of dimethyl sulfoxide solution containing folic acid active ester under stirring conditions, and react in the dark for 12 hours at room temperature;

[0041] 6) Then add NaOH solution (0.1M) dropwise ...

Embodiment 2

[0049] 1) dissolving doxorubicin in water to obtain a doxorubicin solution with a concentration of 5 wt %; dissolving polydopamine in water to obtain a polydopamine solution with a concentration of 3 wt %; precooling the solution for subsequent use;

[0050] 2) Weigh 1.1g of folic acid and place it in a container, dissolve it in anhydrous DMSO, then add 0.72g of EDC and 0.45g of NHS, stir in a dark room at room temperature for 2 hours to fully dissolve the folic acid;

[0051] 3) Obtained the DMSO solution of folic acid active ester, and the solution is wine red;

[0052] 4) Weigh 1.2g chitosan powder, dissolve it in 2% acetic acid solution, mix evenly, and adjust pH=6.0, obtain chitosan solution after ultrasonic;

[0053] 5) In a dark room, slowly add the chitosan solution to 50 mL of dimethyl sulfoxide solution containing folic acid active ester under stirring conditions, and react in the dark for 15 hours at room temperature;

[0054] 6) Then add NaOH solution (0.1M) dropw...

Embodiment 3

[0060] 1) dissolving doxorubicin in water to obtain a doxorubicin solution with a concentration of 6 wt %; dissolving polydopamine in water to obtain a polydopamine solution with a concentration of 4 wt %; precooling the solution for subsequent use;

[0061] 2) Weigh 1.2g of folic acid and place it in a container, dissolve it in anhydrous DMSO, then add 0.77g of EDC and 0.5g of NHS, stir in a dark room at room temperature for 3 hours to fully dissolve the folic acid;

[0062] 3) Obtained the DMSO solution of folic acid active ester, and the solution is wine red;

[0063] 4) Weigh 1.4g of chitosan powder, dissolve in 2.5% acetic acid solution and mix evenly, and adjust pH=6.5, obtain chitosan solution after ultrasonic;

[0064] 5) In a dark room, slowly add the chitosan solution to 60 mL of dimethyl sulfoxide solution containing folic acid active ester under stirring conditions, and react in the dark for 18 hours at room temperature;

[0065] 6) Then add NaOH solution (0.1M) d...

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Abstract

The invention relates to the field of medical materials, and discloses a preparation method of doxorubicin nanoparticles with folate-modified chitosan as a carrier. The preparation method includes thesteps that firstly, folate active ester is prepared, and the folate-modified chitosan is obtained by an amide reaction; a prepared doxorubicin solution and a polydopamine solution are added to a folate-modified chitosan solution, and doxorubicin-folate-chitosan is obtained; and finally, a nucleic acid aptamer AS1411 is mixed with the doxorubicin-folate-chitosan, centrifuged, frozen and dried to obtain the doxorubicin nanoparticles with the folate-modified chitosan as the carrier. According to the preparation method, through preparation of polymer nanoparticles embedded with anticancer drugs,an efficient therapeutic method integrated with tumor thermotherapy and targeting can be realized, the stability of the drugs is improved, active targeting is achieved, the ability to bind to a receptor is improved, and thus the therapeutic effect on cancer cells is greatly improved.

Description

technical field [0001] The invention relates to medical materials, in particular to a method for preparing doxorubicin nanoparticles with folic acid-modified chitosan as a carrier. Background technique [0002] Although gene therapy has made a lot of achievements in basic research, the results of clinical trials are not satisfactory. The existing problems mainly include low gene transfection efficiency, poor vector safety and lack of targeting in gene therapy. Therefore, the development of gene vectors with high-efficiency transfection, safety, low toxicity, and organ or cell specificity has become a bottleneck restricting the development of gene therapy. [0003] Chitosan can be absorbed and utilized by the human body. It has good biocompatibility with human tissues, organs and cells. It is non-toxic and biodegradable. Chitosan oligosaccharides produced during the degradation process do not accumulate in the body and have almost no immunogenicity. , and has a variety of bi...

Claims

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Application Information

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IPC IPC(8): A61K47/54A61K47/69A61K31/704A61K41/00A61P35/00
CPCA61K47/6939A61K47/6935A61K47/549A61K47/545A61K31/704A61K41/0052A61P35/00A61K2300/00
Inventor 王秉徐城锋曹澳陈碧玲万军民彭志勤
Owner ZHEJIANG SCI-TECH UNIV
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