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Gene medicine delivery system and preparation method

A gene drug and delivery system technology, applied in drug delivery, gene therapy, pharmaceutical formula, etc., to achieve the effect of improving the effect, increasing the storage capacity, and increasing the secretion amount

Inactive Publication Date: 2014-03-26
UNIV OF SHANGHAI FOR SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are no research reports on the efficient delivery of double-stranded oligonucleotide drugs by mesoporous silica nanoparticles for cancer treatment at home and abroad.

Method used

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  • Gene medicine delivery system and preparation method
  • Gene medicine delivery system and preparation method
  • Gene medicine delivery system and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Preparation method 1 of double-stranded oligonucleotide drug delivery system:

[0033] 1) Preparation of double-stranded oligonucleotide drug model:

[0034] Will positive chain

[0035] 5'-TCAGAGAGTTAGAGAGTTAGAGAGTCAGAGGTTAGAGAGTTAGAGAGTCAGAGAGTTAGAGAGTTAGAGAG-3' and negative strand

[0036]5'-CTCTCTAACTCTCTAACTCTCTGACTCTCTAACTCTCTAACTCTCTGACTCTCTAACTCTCTAACTCTCTGA-3'

[0037] After hybridization, the obtained double-stranded oligonucleotide drug model was dissolved in ultrapure water to prepare a 1 μg / μl solution, and stored at -20°C for future use.

[0038] 2) Preparation of carrier:

[0039] Step 1: Dissolve 3eq of hexadecyl p-toluenesulfonate (HTATS) and 5eq of triethanolamine (TEA) in 4000eq of water at 80°C, stir to dissolve, and quickly add 50eq of tetraethyl orthosilicate (TEOS), Stirring was continued for 2 hours to obtain white colloidal particles, which were centrifuged and washed with ethanol for several times, then vacuum-dried at 60°C; and finally cal...

Embodiment 2

[0053] Preparation method two of the double-stranded oligonucleotide drug delivery system:

[0054] 1) Preparation of double-stranded oligonucleotide drug model:

[0055] Will positive chain

[0056] 5'-TCAGAGAGTTAGAGAGTTAGAGAGTCAGAGGTTAGAGAGTTAGAGAGTCAGAGAGTTAGAGAGTTAGAGAG-3' and negative strand

[0057] 5'-CTCTCTAACTCTCTAACTCTCTGACTCTCTAACTCTCTAACTCTCTGACTCTCTAACTCTCTAACTCTCTGA-3'

[0058] After hybridization, the obtained double-stranded oligonucleotide drug model was dissolved in ultrapure water to prepare a 1 μg / μl solution and stored at -20°C for future use.

[0059] 2) Preparation of carrier:

[0060] Add 3eq of hexadecyl p-toluenesulfonate (HTATS) and 5eq of triethanolamine into 4000eq of water at 80°C, stir, and quickly add 45eq of tetraethyl orthosilicate (TEOS) and 5eq of (3-aminopropyl) Triethoxysilane, continue to stir for 2 hours to obtain white colloidal particles, centrifuge, wash with ethanol for 5 times, and then vacuum-dry at 60°C. The dried product is r...

Embodiment 3

[0067] Preparation method three of double-stranded oligonucleotide drug delivery system:

[0068] Add the target carrier prepared in Example 1 or Example 2 into ultrapure water to prepare a 1 μg / μl suspension.

[0069] Thaw the prepared ultrapure aqueous solution of the double-stranded oligonucleotide drug model.

[0070] The suspension of the obtained carrier and the ultrapure aqueous solution of the double-stranded oligonucleotide drug were mixed at a mass ratio of 6:1 to prepare the suspension of the two, and then centrifuged after shaking at room temperature for 4 hours in a shaker, and ultrapure water After washing, a mesoporous silica nanoparticle delivery system for double-stranded oligonucleotide drug storage is obtained.

[0071] The obtained delivery system was measured by an ultra-micro spectrophotometer, wherein the storage capacity of the double-stranded oligonucleotide was 145 μg / mg.

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Abstract

The invention provides a gene medicine delivery system comprising a carrier and a gene medicine loaded in the carrier. The gene medicine delivery system is characterized in that the carrier is silane coupling agent-modified mesoporous silica nanoparticles; the gene medicine is stored in pore channels of the mesoporous silica nanoparticles; in the delivery system, 80-300 microgram of gene medicine is stored in 1 mg of silane coupling agent-modified mesoporous silica nanoparticles. By using the delivery system provided by the invention, the gene medicine can be protected against enzymolysis during in vivo delivery, can simultaneously escape from an endosome well and is transferred to cytoplasm.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations and nanometer materials, and in particular relates to a gene drug delivery system and a preparation method using mesoporous silica nanoparticles as carriers. Background technique [0002] At present, the incidence of cancer in the world is rising sharply. The main methods of clinical treatment of cancer at home and abroad are surgery, radiotherapy and drug chemotherapy, but they still cannot effectively prevent the recurrence and metastasis of cancer cells and significantly improve the quality of life and prolong the survival time. . Therefore, cancer treatment is a research hotspot and difficulty in the fields of biology, medicine, and materials all over the world. [0003] Genetic medicine has the characteristics of high efficacy and no side effects, and can inhibit cancer cells from the body's immune system. It is one of the important directions of cancer drug treatment research. Si...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K48/00A61K31/713A61K47/04A61K47/24A61P35/00
Inventor 朱钰方陶翠莲
Owner UNIV OF SHANGHAI FOR SCI & TECH
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