Amphiphilic self-assembled nanomicelle based on nano Low-generation PAMAM (polyamidoamine) dendrimer and application thereof

A nanometer self-assembly, dendrimer technology, which is applied in the directions of non-active ingredients medical preparations, active ingredients-containing medical preparations, and drug combinations, etc. problem, to achieve the effect of improving poor solubility, simple synthesis steps and easy hemolysis

Inactive Publication Date: 2016-08-17
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the reaction process is complicated and the production cost is high, which limits its application to a certain extent.
To sum up, the above studies all use high-generation PAMAM as the research object (the PAMAM generation is 3~6 generations), and the synthesis steps of high-generation PAMAM are cumbersome, resulting in high cost; in addition, the surface of high-generation PAMAM carries a large number of amino groups, which is easy to Interacts with various negatively charged biomembranes in organisms, so there is higher cytotoxicity and more prone to hemolysis

Method used

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  • Amphiphilic self-assembled nanomicelle based on nano Low-generation PAMAM (polyamidoamine) dendrimer and application thereof
  • Amphiphilic self-assembled nanomicelle based on nano Low-generation PAMAM (polyamidoamine) dendrimer and application thereof
  • Amphiphilic self-assembled nanomicelle based on nano Low-generation PAMAM (polyamidoamine) dendrimer and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] Example 1 Synthesis of ursolic acid-modified amphiphilic dendrimer conjugates

[0073] (1) Based on G 0 Synthesis of amphiphilic conjugates of PAMAM dendrimers (G 0 -UA 2 example)

[0074] ① Synthesis of UA-NHS

[0075]Take 2.28g (5mmol) ursolic acid (abbreviation: UA, the same below) in a 150mL round bottom flask, add 50mL tetrahydrofuran, after the UA is dissolved, add 1.15g (10mmol) NHS dissolved in 10mL acetonitrile, and then 2.06 g (10 mmol) of DCC dissolved in 25 mL of tetrahydrofuran was added dropwise at 15°C. Stir magnetically at room temperature for 24 h. After the reaction was completed, the precipitate was removed by filtration, and then tetrahydrofuran was removed by a rotary evaporator to obtain a white powder crude product. Purified UA-NHS was obtained by silica gel column chromatography, and the eluent was dichloromethane:methanol (v / v)=50:1. Its high-resolution mass spectrum see figure 1 .

[0076] ②G O -UA 2 Synthesis

[0077] Take 0.44g (...

Embodiment 2

[0083] Example 2 Synthesis of methotrexate-modified amphiphilic dendrimer conjugates (based on G 1 PAMAM Dendrimer, G 1 -Me 1 example)

[0084] Take 0.182g (0.4mmol) of methotrexate (Methotrexate abbreviation: Me, the same below) in a 150mL round bottom flask, add 50mL of N,N-dimethylformamide to dissolve, add 0.115g dissolved in 10mL of acetonitrile ( 10mmol) NHS, and then dropwise added 0.206g (10mmol) DCC dissolved in 25mL THF at 10~15°C. Stir magnetically at room temperature for 24 h. After the reaction, the precipitate was removed by filtration to obtain an organic solution of the active intermediate product; 1 PAMAM solution in ice bath. At room temperature, avoid light and magnetically stir for 48h. After the reaction, the reaction solution was dialyzed in N,N-dimethylformamide (MWCO=1500) for 1~3 days, then dialyzed in water for 3 days, and freeze-dried to obtain methotrexate-modified amphiphilic dendrimers. molecular conjugates.

Embodiment 3

[0085] Example 3 Synthesis of aspirin-modified amphiphilic dendrimer conjugates (based on G 0 PAMAM Dendrimer, G 0 -ASP 1 example)

[0086] Take 72mg (0.4mmol) of aspirin (Aspirin abbreviation: ASP, the same below) in a 150mL round bottom flask, add 50mL of dichloromethane to dissolve, add 0.115g (10mmol) of NHS dissolved in 10mL of acetonitrile, and then 0.206 g (10 mmol) of DCC dissolved in 25 mL of tetrahydrofuran was added dropwise. Stir magnetically at room temperature for 24 h. After the reaction, the precipitate was removed by filtration to obtain an organic solution of the active intermediate product; 0 PAMAM solution in ice bath. At room temperature, avoid light and magnetically stir for 48h. After the reaction, the reaction solution was dialyzed in N,N-dimethylformamide (MWCO=500) for 1~3 days, then dialyzed in water for 3 days, and freeze-dried to obtain the methotrexate-modified amphiphilic dendrimers. molecular conjugates.

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Abstract

The invention relates to an amphiphilic self-assembled nanomicelle based on nano Low-generation PAMAM (polyamidoamine) dendrimer and application thereof, particularly obtained conjugating low-generation PAMAM dendrimer and a hydrophobic agent and self-assembling in water via ultrasonic vibration. The nanomicelle has active molecules or a prodrug with drug loading capacity; the chemical conjugation of the hydrophobic agent and the low-generation PAMAM dendrimer helps improve the defects of poor solubility of the hydrophobic drug and low bioavailability, and a new idea is provided to solve the problem that traditional clinical chemotherapeutics are high in toxicity and low in safety coefficient; the nanomicelle can also function as a nanocarrier to carry other hydrophobic drugs, enabling joint use of drugs and enhancing therapeutic effect.

Description

technical field [0001] The invention relates to an amphiphilic self-assembled nanomicelle based on a low-generation PAMAM dendrimer and its application. Background technique [0002] Molecular self-assembly (molecular self-assembly) refers to the spontaneous combination of molecules through weak non-covalent interactions between molecules under equilibrium conditions, such as van der Waals forces, hydrogen bonds, hydrophobic interactions, electrostatic interactions, π-π interactions, etc. The process of forming stable aggregates or supramolecules with certain structure and function. Aggregates or supramolecules formed by molecular self-assembly usually have some special properties that single molecules or low-level molecular aggregates do not have, such as optical, electrical, and biological properties. Generally speaking, the self-assembly of molecules has a structure amplification effect, that is, a small change in the molecular structure will cause a huge change in the t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K9/107A61P35/00C08G83/00A61K31/517A61K31/56A61K31/519A61K31/616
CPCA61K31/517A61K31/519A61K31/56A61K31/616C08G83/003A61K2300/00
Inventor 邵敬伟刘亚军陈秀芬
Owner FUZHOU UNIV
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