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Preparation method of amphipathic gama-polyglutanmic acid nanodrug carrier

A nano-drug carrier, polyglutamic acid technology, applied in the field of polymers and medical biomaterials, can solve problems such as limitations, weakened ability to encapsulate drugs, and poor self-assembly performance of modified products, and achieve easy operation and simple process , the effect of controllable output

Active Publication Date: 2012-10-03
NANJING MEDICAL UNIV
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  • Abstract
  • Description
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  • Application Information

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Problems solved by technology

Due to the poor water solubility of polymer polysaccharides, it is often necessary to introduce hydrophilic groups to improve their water solubility, resulting in poor self-assembly properties of modified products, weakened ability to encapsulate drugs and controlled release of drugs, and water-soluble small molecule polysaccharides The drug load is not high, and the application to drug carriers is greatly limited

Method used

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  • Preparation method of amphipathic gama-polyglutanmic acid nanodrug carrier
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  • Preparation method of amphipathic gama-polyglutanmic acid nanodrug carrier

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Experimental program
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Effect test

Embodiment 1

[0048] A method for preparing amphiphilic gamma-PGA nano drug carrier, the method comprises the following steps.

[0049] (1) Dissolve 1g γ-PGA (molecular weight 380KDa, molecular weight distribution coefficient 1.3) in 100mL DMSO (solvent I) at room temperature to form a transparent 10g / L γ-PGA solution.

[0050] (2) Add EDC to the above-mentioned γ-PGA solution in an amount whose ratio to the amount of glutamic acid monomer residues in the γ-PGA obtained in step (1) is 1.2, and heat at room temperature at 500r / min The reaction was activated for 12 hours to form a reaction activation solution.

[0051] (3) Weigh cholesterol according to the ratio of 0.4 to the amount of glutamic acid monomer residues in γ-PGA obtained in step (1), dissolve it in 100 mL of DMSO-pyridine mixed in equal proportions (solvent II) middle.

[0052] (4) Slowly add the cholesterol-containing solution obtained in step (3) dropwise to the reaction activation solution obtained in step (2) within 30 min...

Embodiment 2

[0055] Solvent I uses 1.0mol / L phosphate buffer saline (PBS), the ratio of the amount of catalyst EDC to the amount of glutamic acid monomer residues in the γ-PGA is 2.0, the amount of cholesterol and the amount of glutamic acid in the γ-PGA are Except that the substance amount ratio of the acid monomer residue is 1.0, other conditions are the same as in Example 1. The FTIR and 1 H-NMR such as figure 2 (b) and image 3 (B) shown. according to 1 H-NMR spectrum analysis shows that the degree of substitution of side chains is about 37%.

[0056] The amphiphilicity and critical micelle concentration (CMC) of the γ-PGA graft modified products prepared under this condition were investigated by the pyrene fluorescent probe method, and the pyrene emission spectra were as follows: Figure 4 Shown, the characteristic peak ratio (I 372 / I 385 ) and the logarithmic plot of the concentration of γ-PGA grafted modification Figure 5 , the concentration corresponding to the turning p...

Embodiment 3

[0058] Add the synthetic product of Example 1 to 1 mol / L PBS buffer solution with pH 4.0 so that the concentration of the synthetic product is 1 mg / mL, shake at 25°C for 12 hours at a low speed, and then use a probe-type ultrasonic instrument in an ice-water bath Ultrasonic treatment, working for 2s, stopping for 2s, ultrasonic time for 2min, repeated 3 times to obtain a dispersion of amphiphilic γ-PGA nanomicelles, and then centrifuged at 14000g to collect the precipitate-freeze-drying step to obtain amphiphilic γ-PGA nanomicelle. Electron microscope observation and particle size analyzer results showed that the shape of amphiphilic γ-PGA nanomicelles was relatively regular; the average particle size was about 220nm, and the particle size polydispersity index (PDI) was 0.35.

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Abstract

The invention discloses a preparation method of an amphipathic gama-polyglutanmic acid nanodrug carrier. The preparation method comprises the steps of grafting hydrophobicity group on gama--polyglutanmic acid serving as a main chain, thus obtaining amphipathic gama-polyglutanmic acid derivates with good biocompatibility and degradability, and self assembling in water medium to form nano micelle with particle size of 200-1000nm. The hydrophobic nuclei-hydrophilic shell structure is beneficial to improvement of solubility of hydrophobic drug in water medium, further possibly improves the bioavailability of drugs in the body, and also can be used for load of protein and DNA. The preparation method of the amphipathic gama-polyglutanmic acid nanodrug carrier is simple and practicable, all raw materials can be industrially produced; reproducibility is good; and the amphipathic gama-polyglutanmic acid nanodrug carrier has high drug loading rate, good sustained release effect and intelligent environment response (pH-enzyme complex sensitivity) and other corresponding characteristics, as well as good popularization and application values.

Description

technical field [0001] The invention relates to the field of macromolecules and medical biomaterials, specifically a method for gamma-polyglutamic acid nanoparticles with environmental response characteristics and a hydrophobic core-hydrophilic shell structure. Background technique [0002] At present, drug screening based on functional genomic analysis has obtained various drug active substances, such as proteins, peptides, DNA and other biomacromolecular drugs, but these potential drug candidates are prone to lose drug activity due to the influence of the environment and carrier materials due to their complex structures. , and the use of amphiphilic block / graft polymers is an effective way to achieve drug loading and controlled release in the form of supramolecular self-assembly, especially the use of amphiphilic block / graft polymers to obtain self-assembled drug-loaded nanoparticles Particles are the hotspot of research in this field at present. [0003] From the perspec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K48/00C08G69/48
Inventor 姚俊曹新陈宽婷阮文辉魏钦俊鲁雅洁
Owner NANJING MEDICAL UNIV
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