Composite nano-carrier capable of loading nucleic acid drugs efficiently and preparation method of composite nano-carrier

A nano-carrier and nucleic acid technology, which is applied in the direction of medical preparations of non-active ingredients, pharmaceutical formulas, non-effective ingredients of polymer compounds, etc., can solve the problems of inability to reach the target site, increased thrombus formation, low loading efficiency, etc., to achieve guaranteed In vivo compatibility, easy removal, low cost effect

Active Publication Date: 2013-01-09
ARMY MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Cationic polymer carrier, because it complexes with nucleic acid drugs mainly through electrostatic interaction, the final complex is easily decomplexed by the polyanions that exist in large quantities in blood and extracellular fluid, so that it cannot reach the target site to achieve ideal transfection
In addition, for low-molecular-weight nucleic acid drugs (such as antisense nucleotides, siRNA and microRNA), their rigid structure and low charge density often lead to incomplete aggr

Method used

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  • Composite nano-carrier capable of loading nucleic acid drugs efficiently and preparation method of composite nano-carrier
  • Composite nano-carrier capable of loading nucleic acid drugs efficiently and preparation method of composite nano-carrier
  • Composite nano-carrier capable of loading nucleic acid drugs efficiently and preparation method of composite nano-carrier

Examples

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Example Embodiment

[0033] Example 1

[0034] First, 1 nmol of pDNA encoding β-galactosidase was dissolved in 100 μl of water to obtain the internal aqueous phase; 50 mg of polylactic acid (PLA, molecular weight 15 kDa) and 0.5 mg of branched polyethyleneimine with molecular weight of 800 Da were dissolved in 1 The organic phase is obtained in ml of dichloromethane; then the internal water phase is emulsified in the organic phase under the ultrasound of the probe to form water-in-oil colostrum, which is emulsified in 10 ml of 0.5% by mass under ultrasound of the probe A water-in-oil-in-water double emulsion is obtained in an aqueous solution of polyvinyl alcohol (molecular weight 8.8 kDa, degree of hydrolysis 88%); the resulting double emulsion is magnetically stirred at room temperature to volatilize and remove the organic solvent from the organic phase. After the nanoparticles are solidified, they are centrifuged. After washing with double distilled water, a composite nanocarrier loaded with pDNA ...

Example Embodiment

[0035] Example 2

[0036] First, 0.5 nmol Bcl-2 antisense oligonucleotide was dissolved in 100 μl of water to obtain the internal aqueous phase; 50 mg of polylactide-glycolide (PLGA, lactic acid / glycolic acid molar ratio 50:50, molecular weight 20 kDa) and 2.5 mg of branched polyethyleneimine with a molecular weight of 1.8 kDa was dissolved in 1 ml of dichloromethane to obtain the organic phase; then the internal water phase was emulsified in the organic phase under the ultrasonic action of the probe to form water-in-oil colostrum. The probe was emulsified in 20 ml of 1% polyvinyl alcohol (molecular weight 8.8 kDa, hydrolysis degree 88%) aqueous solution under ultrasound to obtain a water-in-oil-in-water double emulsion; the resulting double emulsion was removed by magnetic stirring at room temperature The organic solvent of the organic phase, after the nanoparticles are solidified, centrifuged and washed with double distilled water, the composite nanocarrier loaded with Bcl-2 an...

Example Embodiment

[0037] Example 3

[0038] First, 1 nmol Bcl-2 antisense oligonucleotide was dissolved in 150 μl water to obtain the internal aqueous phase; 50 mg polylactide-glycolide (PLGA, lactic acid / glycolic acid molar ratio 75:25, molecular weight 25 kDa) and 5 mg of branched polyethyleneimine with a molecular weight of 10 kDa was dissolved in 1 ml of chloroform to obtain an organic phase; then the internal water phase was emulsified in the organic phase under ultrasound of the probe to form water-in-oil colostrum, which was used in the ultrasound of the probe Under emulsification in 50 ml of 0.8% polyvinyl alcohol (molecular weight 25 kDa, hydrolysis degree 80%) aqueous solution to obtain a water-in-oil-in-water double emulsion; the resulting double emulsion is magnetically stirred at room temperature to volatilize and remove the organic phase After the nanoparticles are solidified, they are centrifuged and washed with double distilled water to obtain composite nanocarriers loaded with Bcl...

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Abstract

The invention relates to a composite nano-carrier capable of loading nucleic acid drugs efficiently and a preparation method of the composite nano-carrier. The composite nano-carrier is composed of a degradable organic material and polyamine with different molecular weights, wherein the mass ratio of the polyamine with different molecular weights to the degradable organic material is (0.005: 100)-(3:7), the composite nano-carrier is spherical, the particle size of the composite nano-carrier ranges from 80 nm to 950 nm, and the nucleic acid drugs are distributed in the composite nano-carrier uniformly. The preparation method of the composite nano-carrier includes steps of firstly, dissolving the nucleic acid drugs into water to obtain internal water phase, dissolving the degradable organic material and the polyamine with different molecular weights into organic solvent to obtain organic phase, taking polyving alcohol aqueous solution as external water phase; secondly, emulsifying the internal water phase into the organic phase under ultrasonic action of a probe so as to form water-in-oil colostrum, emulsifying the water-in-oil colostrum into the external water phase under ultrasonic action of the probe so as to obtain oil-in-water multiple emulsion, stirring the multiple emulsion by magnetic force at room temperature so as to remove the organic solvent in the organic phase by volatilizing, performing centrifugal separation after nano-particles are solidified, washing the nano-particles with double distilled water so as to obtain the composite nano-carrier capable of loading nucleic acid drugs.

Description

technical field [0001] The invention relates to a composite nanocarrier capable of efficiently loading nucleic acid drugs and a preparation method thereof. Background technique [0002] Gene therapy by expressing biologically active substances, inhibiting dysfunctional genes that lead to genetic disorders or uncontrolled cell proliferation is a powerful method for the prevention and treatment of many major diseases such as genetic defect diseases, infections, tumors and cardiovascular diseases. At present, the lack of safe and effective gene carriers is the main bottleneck limiting the wide application of gene therapy in clinic. Although viral vectors, such as adenoviruses, retroviruses, and lentiviruses, have high transfection efficiencies, their potential immunogenicity, production control, and cost hinder their application. Compared with viral vectors, non-viral vectors have many advantages, such as low immunogenicity and toxicity, easy synthesis and mass production, low...

Claims

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Application Information

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IPC IPC(8): A61K47/40A61K47/34A61K48/00
Inventor 张建祥李晓辉窦寅李淑慧
Owner ARMY MEDICAL UNIV
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