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Polyethylene glycol modified calcium-based nano-drug delivery particle, preparation method thereof and application

A polyethylene glycol and nano-medicine technology, applied in the field of biomedicine, can solve problems such as easy agglomeration, poor controllability of calcium silicate particle size, poor dispersion, etc.

Active Publication Date: 2017-09-15
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The calcium silicate particles prepared by the traditional precipitation method have poor particle size controllability, are easy to agglomerate in aqueous solution, and have poor dispersibility

Method used

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  • Polyethylene glycol modified calcium-based nano-drug delivery particle, preparation method thereof and application
  • Polyethylene glycol modified calcium-based nano-drug delivery particle, preparation method thereof and application
  • Polyethylene glycol modified calcium-based nano-drug delivery particle, preparation method thereof and application

Examples

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Effect test

Embodiment 1

[0092] Example 1 Preparation of calcium silicate-microcircular DNA nanoparticles without polyethylene glycol (PEG) modification

[0093] One embodiment of the present invention provides a method for preparing calcium silicate-microcircular DNA nanoparticles without polyethylene glycol (PEG) modification, comprising the steps of:

[0094] (1) Mix 10 μl DNA solution (0.5 μg / μl) with 10 μl PEI25K cationic polymer solution (1.3 μg / μl), and incubate for 30 minutes; then, add 80 μl calcium chloride solution (500 mM, pH 10.0), and use After blowing with a pipette to make it evenly mixed, add it dropwise to 5ml of the organic phase under stirring (the organic phase is prepared by mixing cyclohexane and polyethylene glycol nonylphenyl ether 520 (IgepalCO-520) at a volume ratio of 7 / 3) ), stirred for 1h to form microemulsion A;

[0095] (2) Add tetraethyl orthosilicate (TEOS) dropwise to the microemulsion A obtained in step (1) under stirring, and stir for one hour to form microemulsio...

Embodiment 2

[0103] Preparation of Calcium Silicate-microcircular DNA Nanoparticles Modified by Example 2 Polyethylene Glycol (PEG)

[0104] One embodiment of the present invention provides a method for preparing calcium silicate-microcircular DNA nanoparticles modified by polyethylene glycol (PEG), comprising the steps of:

[0105] (1) Mix 10 μl DNA solution (0.5 μg / μl) with 10 μl polyethyleneimine (PEI25K) solution (1.3 μg / μl) and incubate for 30 minutes; then add 80 μl calcium chloride solution (500 mM, pH 10.0 ), mix it evenly with a pipette gun, and add it dropwise to 5ml of the organic phase under stirring (the organic phase is cyclohexane and polyethylene glycol nonylphenyl ether 520 (Igepal CO-520) in a volume ratio of 7 / 3 mixed), stirred for one hour to form microemulsion A;

[0106] (2) Add 500 μl tetraethyl orthosilicate (TEOS) dropwise to the microemulsion A obtained in step (1) under stirring, after stirring for 4 hours, add 10 μl calcium chloride solution (500 mM, pH 10 .0...

Embodiment 3-4

[0119] In order to further illustrate the beneficial effects of the present invention, repeat the experimental steps of Example 2, the concentration and volume of each drug in steps (1)-(4) in Example 2 are replaced with each drug shown in Table 1 Example 3 respectively. The concentration and volume of the drug were used to obtain polyethylene glycol (PEG)-calcium silicate-microcircular DNA nanoparticles.

[0120] In order to further illustrate the beneficial effects of the present invention, repeat the experimental steps of Example 2, the concentration and volume of each drug in steps (1)-(4) in Example 2 are replaced by each drug shown in Table 3 Example 4 respectively. The concentration and volume of the drug were used to obtain polyethylene glycol (PEG)-calcium silicate-microcircular DNA nanoparticles.

[0121] In order to further illustrate the beneficial effect of the present invention, repeat the step of embodiment 2, replace the orthoethyl silicate (TEOS) in the step (...

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Abstract

The invention provides a polyethylene glycol modified calcium-based nano-drug delivery particle, a preparation method thereof and an application. The particle size of the polyethylene glycol modified calcium-based nano-drug delivery particle is 20-200 nanometers, the polyethylene glycol modified calcium-based nano-drug delivery particle comprises a first target delivery material and a calcium-based particle wrapped with the first target delivery material, the surface of the calcium-based particle is modified with polyethylene glycol, the first target delivery material comprises a biological drug, a chemical drug or a second target delivery material entrapped with nucleic acid fragments, and the second target delivery material entrapped with the nucleic acid fragments is a cationic polymer, polypeptide, polyamino acid or transfection reagent wrapped, combined or blended with the nucleic acid fragments. The particle size of the nano-particle can be controlled in the preparation process of the polyethylene glycol modified calcium-based nano-drug delivery particle, the surface of the calcium-based particle is protected by a polyethylene glycol chain, so that in vivo circulation time is prolonged, and the particle is low in preparation cost, low in toxicity, safe and effective.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a polyethylene glycol-modified calcium-based nano-medicine delivery particle and a preparation method and application thereof. Background technique [0002] Gene therapy holds promise for many serious acquired and congenital diseases. However, the lack of a safe, efficient and stable gene delivery system is the biggest obstacle preventing gene therapy from entering the clinic. Viral vectors are a common type of gene vectors, which use viruses to infect host cells to introduce foreign genes into host cells. Generally include adenovirus vector (AV), adeno-associated virus vector (AAV), retrovirus and so on. Although viral vectors have high transfection efficiency, the capacity of viral vectors to load genes is limited, and there are potential biological safety hazards due to immunogenicity, so the clinical application of viral gene vectors is also difficult to promote. In recent years...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/60A61K48/00A61K47/10A61K9/51
CPCA61K9/5115A61K47/10A61K48/0041
Inventor 赵静王志勇黄萍杨磊何成宜陈志英
Owner SHENZHEN INST OF ADVANCED TECH
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