Shell-crosslinked polymeric micelles by using metal nanoparticles as crosslinking agent

A technology of metal nanoparticles and polymer glue, which is applied in the direction of drug combination, drug delivery, medical preparations of non-active ingredients, etc., can solve the problem of non-degradability of cross-linked polymer micelles, and meet the stability requirements , the effect of good biocompatibility

Inactive Publication Date: 2010-06-30
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although these cross-linking methods can improve the stability of polymer micelles, the formed cross-linked polymer micelles are not degradable, and the biocompatibility or safety of cross-linked copolymer micelles needs to be verified

Method used

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  • Shell-crosslinked polymeric micelles by using metal nanoparticles as crosslinking agent
  • Shell-crosslinked polymeric micelles by using metal nanoparticles as crosslinking agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] (1) Amphiphilic block polymer R-(CH 2 CH 2 O) m CH 2 CH 2 OCOCH 2 CH 2 SH terminal thiol modification:

[0030] R in the block polymer is polypropylene oxide, and the amphiphilic block polymer is used as a raw material. The specific synthesis steps are as follows:

[0031] a) Add 1 part by weight of 3,3'-dithiodipropionic acid and 10 parts by weight of thionyl chloride to 1000 parts by weight of tetrahydrofuran solvent, heat to 60 ° C, react for 4 hours, and remove unreacted chloride under reduced pressure Sulfoxide and solvent, obtain intermediate product 3,3'-dithiodipropionyl chloride;

[0032] b) 1 part by weight of the intermediate product 3,3'-dithiodipropionyl chloride was dissolved in 50 parts by weight of tetrahydrofuran solvent to obtain solution A;

[0033] c) 1 weight part of precursor polymer (CH 2 CH(CH 3 )O) n -(CH 2 CH 2 O) m CH 2 CH 2 OH was dissolved in 50 parts by weight of tetrahydrofuran solvent to obtain solution B, wherein m is an ...

Embodiment 2

[0041] (1) Amphiphilic block polymer R-(CH 2 CH 2 O) m CH 2 CH 2 OCOCH 2 CH 2 SH terminal thiol modification: same as in Example 1. NMR and IR confirmed that the obtained product had the expected structure.

[0042] (2) Preparation of silver nanoparticles with a particle size of 3.5nm: 2.06mL of 10mg / mL silver nitrate aqueous solution was added to 200mL of sodium citrate (14.7mg) aqueous solution, and 6mL of iced sodium borohydride (22.8mg ) solution, stirred and reacted for 1h. Ultraviolet and transmission electron microscopy confirmed that the obtained silver nanoparticles had a regular structure, were uniformly dispersed and had a particle size of about 3.5nm.

[0043] (3) Cross-linking of silver nanoparticles on the surface of block polymer micelles: under the protection of nitrogen, the polymer was made into a micellar aqueous solution at 37° C., and the deoxidized silver nanoparticles were added dropwise to the above solution, and stirred overnight. Taking the c...

Embodiment 3

[0045] (1) Amphiphilic block polymer R-(CH 2 CH 2 O) m CH 2 CH 2 OCOCH 2 CH 2 SH terminal thiol modification: same as in Example 1. NMR and IR confirmed that the obtained product had the expected structure.

[0046] (2) Preparation of platinum nanoparticles with a particle size of 3.5nm: 2.06mL of 10mg / mL platinum nitrate aqueous solution was added to 200mL of sodium citrate (14.7mg) aqueous solution, and 6mL of iced sodium borohydride (22.8mg ) solution, stirred and reacted for 1h. Ultraviolet and transmission electron microscopy confirmed that the obtained platinum nanoparticles had a regular structure, were uniformly dispersed and had a particle size of about 3.5nm.

[0047] (3) Cross-linking of platinum nanoparticles on the surface of the block polymer micelles: under nitrogen protection, the polymer was made into a micellar aqueous solution at 37° C., and the deoxygenated platinum nanoparticles solution was added dropwise to the above solution, and stirred overnig...

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Abstract

The invention discloses a shell-crosslinked polymeric micelles by using metal nanoparticles as a crosslinking agent and a preparation method thereof. The shell-crosslinked polymeric micelles by using metal nanoparticles as a crosslinking agent consist of polymer micelles and the metal nanoparticles coated on the shells of the polymer micelles. The method for preparing the shell-crosslinked polymeric micelles comprises the following steps: performing functionalized modification on the tail end of an amphiphilic polymer so as to form a functional group capable of reacting with the metal nanoparticles; self-assembling the amphiphilic polymer containing the reactive functional group to form polymeric micelles, and positioning the reactive functional group on the shell surfaces of the polymeric micelles; adding the metal nanoparticles and chemically combining the metal nanoparticles with the reactive functional group so as to form the polymeric micelles crosslinked by the metal nanoparticles. The obtained polymeric micelles have excellent biocompatibility, anti-dilution stability and bio-responsibility, and have wide application prospect in gene and medicament delivery, biosensor and other fields.

Description

technical field [0001] The invention relates to a compound and a preparation method, in particular to a shell cross-linked polymer micelle with metal nanoparticles as a cross-linking agent and a preparation method. Background technique [0002] Polymeric micelles have significant advantages as carriers of anticancer drugs [Eur J Pharm Biopharm 1999, 48, 101]. Compared with other means of solubilizing drugs, the advantages of the polymer micelle-based method stem from its several main properties: polymer micelles can dissolve hydrophobic drugs that are poorly soluble in water in their hydrophobic cores; The shell can prevent drugs from being absorbed by RES (reticuloendothelial system) or MPS (monocyte phagocyte system) and prolong their systemic circulation time; in addition, since tumor vessels are looser than normal vessels, their selective permeability is lower, and they promote Factors such as high vascular permeability and lack of lymphatic drainage in tumors allow pol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K47/34A61K47/32A61K47/28C08G65/334C08G65/32A61P35/00A61K47/10
Inventor 徐建平计剑杨曦吕丽萍魏雨徐方明
Owner ZHEJIANG UNIV
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