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A preparation method for a nano drug, the obtained nano drug and an application thereof

A kind of nano-drug and nano-technology, which is applied in the direction of drug combination, pharmaceutical formula, medical preparations of non-active ingredients, etc., to improve the ability of tumor accumulation, prevent early leakage, and enhance the effect of anti-tumor effect

Inactive Publication Date: 2019-05-07
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the currently reported nano-drug delivery system with redox response only achieves the controlled release of drugs in tumor cells, but ignores the difference in the concentration of GSH and other substances in the tumor microenvironment and blood circulation, and this difference is important for improving high The enhanced permeability and retention effect (EPR effect) and even the tumor treatment effect play a very important role

Method used

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  • A preparation method for a nano drug, the obtained nano drug and an application thereof
  • A preparation method for a nano drug, the obtained nano drug and an application thereof
  • A preparation method for a nano drug, the obtained nano drug and an application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] 10mg PCL 90 -b-PAA 17 Dissolve in 5mL N,N-dimethylformamide (DMF), and add 40mL deionized water after complete dissolution. Add 0.1mL NH 3· h 2 O and 0.04mL MPTMS, stirred at room temperature for 24h. Transfer the stirred solution to a dialysis bag with a molecular weight cut-off of 14,000, and replace the dialysis water every 4 to 6 hours. Dialyze for more than 48 hours to remove organic solvents, ammonia water, unencapsulated drugs and unreacted MPTMS. get to income Add 60mg mPEG-SH (M.W.=10000) and 2mg I 2 , reacted for 24h to get Add MES and NaCl to make MES buffer solution, adjust the pH to about 5.2 with NaOH, add 6 μmol EDCI, NHS-Sulfo, PEI (M.W.=600), stir for 24 hours, dialyze for 24 hours to remove small molecules, and obtain the final

[0029] Figure 2a shows that the average particle size of PCL-b-PAA micelles is 113.4 nm, Figure 2b show The average particle size is 116.5nm, Figure 2c show The average particle size is 140.2nm, Figu...

Embodiment 2

[0034] The implementation method and basic formula are the same as in Example 1, only the molecular weight of mPEG-SH (5k, 10k, 20k) is changed, and the molar amount of the feed is kept at 6 μmol, and finally PEG-SH with different lengths is obtained.

[0035] Figure 7 are PEG-modified with different lengths The particle size distribution diagram. Obviously, as the molecular weight of PEG increases, the particle size of the obtained nanomaterials increases accordingly.

Embodiment 3

[0037] The implementation method and the basic formula are the same as in Example 1, only the feeding amount (1.5, 3, 6, 9, 12, 18 μmol) of the PEI reacted with the carboxyl group is changed, and finally different PEI modification amounts are obtained.

[0038] Figure 8a-Figure 8f are different amounts of PEI modification transmission electron microscope image. Obviously, the morphology of nanomaterials does not change much when modified with different amounts of PEI.

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Abstract

The invention relates to a preparation method for a nano drug. The method includes forming a drug-loaded nano-micelle by an amphiphilic block copolymer containing a carboxyl group in a hydrophilic chain segment and a hydrophobic drug through self-assembly; obtaining a disulfide-bonded, sulfhydryl and carboxyl bi-functionalized first organosilicon nanohybrid micelle through the reaction of the drug-loaded nano-micelle and a sulfhydryl or disulfide bond containing silane coupling agent; obtaining a polyethylene glycol and carboxyl bi-functionalized second organosilicon nanohybrid micelle throughthe oxidation reaction of the first organosilicon nanohybrid micelle; and obtaining the polyethylene glycol and polyethyleneimine bi-functionalized nano drug through the amide reaction of the secondorganosilicon nanohybrid micelle. The obtained nano drug and an application thereof are also related. The enrichment and retention of the nano drug on tumors can be promoted according to the first level response of the nano drug, and the responsive release of anti-cancer drugs can also be promoted through second level response, so that more efficient chemotherapy can be realized.

Description

technical field [0001] The invention relates to the field of nano-biomedicine, in particular to a preparation method of nano-medicine, the obtained nano-medicine and its application. Background technique [0002] In recent years, using the self-assembly behavior of amphiphilic block copolymers in water to load hydrophobic chemotherapeutic drugs with therapeutic functions in its hydrophobic core to achieve tumor chemotherapy has attracted more and more attention of researchers (Biomaterials, 2017 , 113, 243-253; ACS Appl. Mater. Interfaces, 2015, 7, 9211-9227; Adv. Mater., 2017, 29, 1702342). Although these nanomedicines increase the tumor inhibition rate and reduce toxic side effects through the enhanced penetration and retention effect (EPR), due to the existence of multiple biological barriers, especially the blood tumor barrier, the usual nanomedicines are still not enough to increase the accumulation of tumor sites. and drug loading efficiency (Clin. Cancer. Res., 2016,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/60A61K47/59A61K47/69A61K9/107A61K47/34A61K47/24A61K31/4745A61K31/12A61P35/00
Inventor 李永生贾晓博牛德超
Owner EAST CHINA UNIV OF SCI & TECH
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