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Intelligent amphiphilic polymer nano micelle and preparation method and application thereof

A technology of amphiphilic polymers and nanomicelles, applied in the fields of polymer chemistry and biomedical engineering, can solve the problems of simultaneous chemotherapy and photothermal therapy, poor biocompatibility, short cycle time, etc., and is easy to promote Easy application, easy operation, good stability effect

Active Publication Date: 2014-04-02
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To solve the problems of poor biocompatibility of nano-drug carriers in the prior art, short circulation time in the body, poor targeting, and inability to achieve chemotherapy and photothermal therapy at the same time

Method used

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  • Intelligent amphiphilic polymer nano micelle and preparation method and application thereof
  • Intelligent amphiphilic polymer nano micelle and preparation method and application thereof
  • Intelligent amphiphilic polymer nano micelle and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] The preparation method of TP-PEG-b-PLH-b-PLC-HPPr smart amphiphilic polymer nanomicelles includes the following steps:

[0051] (a) Preparation of polymer PEG-b-PLH(DNP)-b-PLC(Trt)

[0052] The polymerization tube was evacuated and filled with nitrogen for protection, and 1g of HOOC-PEG-NH with a molecular weight of 2000 2 Dissolve it with 25mL DMF and add it to the polymerization tube, press His(DNP)-NCA monomer and HOOC-PEG-NH 2 Add His(DNP)-NCA monomer at a molar ratio of 20:1 React at constant temperature under nitrogen protection for 48 hours, then press Cys(Trt)-NCA monomer With HOOC-PEG-NH 2 Cys(Trt)-NCA monomer was added at a molar ratio of 10:1, and the reaction was continued at a constant temperature for 24 hours under the protection of nitrogen. After the reaction, 20 times of ether was added to precipitate, filtered and dried to obtain PEG-b-PLH(DNP) -b-PLC(Trt) triblock polymer;

[0053]

[0054] (b) Preparation of polymer PEG-b-PLH(DNP)-b-PLC(Trt)-HPPr

[0055] ...

Embodiment 2

[0062] The preparation method of intelligent amphiphilic polymer nano micelles loaded with nano gold includes the following steps:

[0063] Under the protection of nitrogen, 0.1 g of TP-PEG-b-PLH-b-PLC-HPPr triblock polymer was dissolved in 15 mL of dimethyl sulfoxide, and 3 times the molar amount of the repeating unit of the PLC segment was added. Sugar alcohol, react at 40℃ for 3 hours, then add 30 times of ether, precipitate, filter and dry to obtain TP-PEG-b-PLH-b-PLC-HPPr triblock polymer with PLC side chain sulfhydryl group. This TP-PEG-b-PLH-b-PLC-HPPr triblock polymer is dissolved in tetrahydrofuran under the protection of nitrogen to obtain a mixed solution, and the obtained mixed solution is dropped dropwise to contain 0.01g of nano-gold under vigorous stirring After stirring the particles in 10mL aqueous solution at room temperature (25°C) for 12 hours, centrifugation to remove uncoated gold nanoparticles, then rotary evaporation to remove excess tetrahydrofuran, and t...

Embodiment 3

[0065] The preparation method of drug-loaded smart amphiphilic polymer nanomicelles loaded with nano gold and paclitaxel includes the following steps:

[0066] The smart amphiphilic polymer nanomicelles loaded with gold nanoparticles prepared in Example 2 were dispersed in water to obtain a polymer solution. In the polymer solution, TP-PEG-b-PLH-b-PLC-HPPr The content of the segment polymer is 0.005g / mL;

[0067] Weigh 0.01g of paclitaxel and completely dissolve it in DMSO to form a uniform and transparent solution. Add this solution dropwise to 10mL of the polymer solution obtained above, stir at room temperature for 2 hours, and place it in a dialysis bag with a molecular weight cutoff of 3500. Then it was dialyzed in 200 times the amount of water for 24 hours, and the water was changed every 2 hours; after the dialysis, the drug-loaded smart amphiphilic polymer nanomicelles loaded with nano-gold and paclitaxel were obtained. DLS was used to detect the loaded nano-gold and paclit...

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Abstract

The embodiment of the invention provides an intelligent amphiphilic polymer nano micelle which comprises components of targeted peptide-polyethylene glycol-b-polyhistidine-b-polycysteine-phenylpropionic acid, wherein targeted peptide is a polypeptide sequence capable of mediating an active targeting transferring function, a polyethylene glycol chain segment is amino-polyethylene glycol-carboxyl, a carboxyl terminal of the polyethylene glycol chain semgnet is connected with the targeted peptide, an amino terminal of the polyethylene glycol is connected with a polyhistidine chain segment, the other terminal of the polyhistidine chain segment is connected with a polycysteine chain segment, and the phenylpropionic acid as a terminal capping reagent is connected with amino at the tail terminal of the polycysteine chain segment. The intelligent amphiphilic polymer nano micelle has better biocompatibility, can be biologically degraded and metabolized, has a pH sensitive response and an active targeting transferring function, can be used as a hydrophobic drug carrier, and can also load gold nanoparticles to realize photo-thermal treatment of tumors. The embodiment of the invention further provides a preparation method and application of the intelligent amphiphilic polymer nano micelle.

Description

Technical field [0001] The invention relates to the fields of polymer chemistry and biomedical engineering, in particular to a smart amphiphilic polymer nano micelle and its preparation method and application. Background technique [0002] With the development of nano-biotechnology, traditional single-function, simple amphiphilic block polymer micelles can no longer adapt to their application in the complex and changeable human physiological environment. Multifunctional intelligent responsive nano-micelle particles have gradually become The research hotspot is that such nanomicelles can change their structure or performance with changes in the human body’s environment or stimuli, so that they can transport the loaded drugs smoothly through various physiological barriers in the body to reach the target site and achieve targeted delivery. Drugs, reduce adverse drug reactions and improve drug efficacy. If chemotherapy is supplemented with photothermal therapy or other treatments, it...

Claims

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Application Information

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IPC IPC(8): A61K47/42A61K9/107A61P35/00C08G65/48C08G69/48C08G69/42A61K41/00
Inventor 蔡林涛易虎强敖丽娇马轶凡刘朋谢高峰
Owner SHENZHEN INST OF ADVANCED TECH
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