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A kind of double sensitive responsive polymer nanomicelle and its preparation method and application

A nano-micelle and polymer technology, which is applied in the fields of polymer chemistry and biomedical engineering, can solve the problems of poor targeting, poor controlled release effect, and low bioavailability of nano-drug carriers, and achieve the goal of solving targeted problems. Not strong, the preparation method is simple and easy, and the effect of prolonging the cycle time

Active Publication Date: 2015-09-09
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In view of this, the present invention aims to provide a biodegradable, stable, active targeted delivery function, capable of loading hydrophobic small molecule drugs, and capable of realizing charge reversal and reduction response double sensitive responsive polymer nanomicelle Drug carrier to solve various problems such as poor targeting, low bioavailability, poor stability, and poor controlled release effect of nano drug carriers in the prior art

Method used

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  • A kind of double sensitive responsive polymer nanomicelle and its preparation method and application
  • A kind of double sensitive responsive polymer nanomicelle and its preparation method and application
  • A kind of double sensitive responsive polymer nanomicelle and its preparation method and application

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Embodiment 1

[0040] The preparation method of Tutane-PLL (FA / DMMA)-b-PLC double sensitive response type polymer nano-micelle, comprises the steps:

[0041] (a) Preparation of polymer Tutane-PLL(Z)-b-PLC(Z)

[0042] Vacuum the polymerization tube and fill it with nitrogen protection, absorb 1g Tutane ( ) mixed with 30mL DMF and added to the polymerization tube, press Lys(Z)-NCA monomer Add the Lys(Z)-NCA monomer at a molar ratio of 30:1 to Tutane, continue the constant temperature reaction under nitrogen protection for 36 hours, and press the Cys(Z)-NCA monomer Add Cys(Z)-NCA monomer with a molar ratio of 10:1 to Tutane, and continue to react at constant temperature for 72 hours under nitrogen protection. After the reaction, add 30 times of diethyl ether to precipitate, filter, and dry to obtain Tutane-PLL(Z) -b-PLC(Z) block polymer in,

[0043] (b) Preparation of polymer Tutane-PLL-b-PLC

[0044] Dissolve the Tutane-PLL(Z)-b-PLC(Z) block polymer obtained above in trifluoroacetic...

Embodiment 2

[0051] The preparation method of the drug-loaded double-sensitive responsive polymer nanomicelle loaded with paclitaxel comprises the following steps:

[0052] Weigh 10 mg of Tutane-PLL (FA / DMMA)-b-PLC polymer, 2 mg of paclitaxel, dissolve in 10 mL of dimethyl sulfoxide, and sonicate at room temperature for 5 min to fully dissolve the drug paclitaxel and the polymer to form a uniform, transparent organic Phase solution, the obtained organic phase solution was placed in a dialysis bag with a molecular weight cut-off of 2000, and then dialyzed in 1L of NaOH water with pH=8.5 for 12 hours, and the water was changed every 2 hours. The aqueous solution of drug-loaded micelles is the drug-loaded dual-sensitive responsive polymer nanomicelle loaded with paclitaxel. The Zeta potential of the aqueous solution is -25.6mv, and the particle size of the drug-loaded dual-sensitive responsive polymer nanomicelle is detected by DLS , the detection result is as figure 2 As shown, the measure...

Embodiment 3

[0054] The preparation method of the drug-loaded double-sensitive responsive polymer nanomicelle loaded with doxorubicin comprises the following steps:

[0055] Weigh 80 mg of Tutane-PLL (FA / DMMA)-b-PLC polymer, 5 mg of doxorubicin, dissolve in 100 mL of DMF, and ultrasonicate for 3 min at room temperature to fully dissolve the drug and the polymer to form a uniform, transparent organic phase solution; The obtained organic phase solution was placed in a dialysis bag with a molecular weight cut-off of 2000, and then dialyzed in 2 L of NaOH aqueous solution with pH=8.5 for 18 hours, and the water was changed every 4 hours; after the dialysis, the drug-loaded micelles formed in the dialysis bag were collected aqueous solution, and then freeze-dried to obtain a powdery solid, which is the drug-loaded double-sensitive responsive polymer nanomicelle loaded with doxorubicin. The average particle size measured by DLS is 61.6nm, and the particle size dispersion is relatively uniform. ...

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Abstract

The embodiment of the invention provides a dual-sensing response type polymer nano-micelle. The component of the nano-micelle is n-butylamine-polylysine (folic acid / 2,3-dimethylmaleic anhydride)-b-polycysteine, wherein n-butylamine is connected with one end of a polylysine chain segment through an amido bond, and the other end of the polylysine chain segment is connected with a polycysteine chain segment; folic acid is connected with the amidogen of the side chain part of the polylysine chain segment through the amido bond; 2,3-dimethylmaleic anhydride is connected with the rest amidogen of the side chain of the polylysine chain segment in an amido bond manner. The dual-sensing response type polymer nano-micelle can be used as a carrier of a hydrophobic drug, is biodegradable and stable in property, has a function of positive target transfer, and can realize charge reversal and reducing response. The embodiment of the invention also provides a preparation method and application of the dual-sensing response type polymer nano-micelle.

Description

technical field [0001] The invention relates to the fields of macromolecule chemistry and biomedical engineering, in particular to a double-sensitive responsive polymer nanomicelle and its preparation method and application. Background technique [0002] Tumor is a frequently-occurring disease that threatens human health, and chemotherapy is one of the important methods to treat tumor. However, most tumor chemotherapy drugs have strong tissue and organ side effects, lack of tumor targeting, and fail to achieve the expected efficacy. Nanocarriers have become the current research hotspot in tumor treatment due to their advantages of increasing drug concentration in tumor cells, solubilizing drugs and improving drug bioavailability through active or passive targeting to tumors, among which polymer micelles are the research focus. One of the most numerous nanocarriers. [0003] With the deepening of research, the traditional single and simple nano-drug carrier system can no lo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/34A61K9/107A61P35/00C08G69/48C08G69/42A61K31/337A61K31/704
Inventor 蔡林涛易虎强龚萍谢高峰刘朋王碧
Owner SHENZHEN INST OF ADVANCED TECH
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