Nucleic acid delivery system as well as preparation method and application thereof

A delivery system and nucleic acid technology, applied in the field of nucleic acid delivery system and its preparation, to achieve the effects of improving cell uptake efficiency, protecting molecular stability, and improving loading efficiency

Active Publication Date: 2021-07-09
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there are still very limited strategies on how to improve the stability of nucleic acid drugs during delivery and the efficiency of cell transfection. Polyester polymers also have certain potential as delivery materials for siRNA drugs, but more related research is still needed. It is necessary to explore the feasibility of such materials for siRNA drug delivery

Method used

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  • Nucleic acid delivery system as well as preparation method and application thereof
  • Nucleic acid delivery system as well as preparation method and application thereof
  • Nucleic acid delivery system as well as preparation method and application thereof

Examples

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Effect test

Embodiment 1

[0062] The present invention provides a nucleic acid delivery system, named P3HB3HV3HHHX / DOPC / siRNA-1 nanoparticles, and the preparation method thereof is as follows:

[0063] (1) The amount of 26.5 μL of 50 mg / ml of DOPC chloroform solution was added to the glass tube, placed in a fume hood, after the solvent was completely wary, and 662.5 μL of 1% P3HB3HV3HHHHHHHHX dichloromethane solution was added. A siRNA solution (solvent was DEPC water) was taken by 20 μl of the concentration of 50 nmol / ml, and the DEPC water was added to 331.3 μL, and the above glass bottles were added. Ultrasound 5min (2S per ultrasonic 3S) is ultrasonic 5min (2S per ultrasonic 3S), and 2S per ultrasonic 3S is paused 2S).

[0064] (2) 1987.5 μL of 2% (W / W) of PVA aqueous solution was added to the ceremonial solution, and the temporal 30s, 65W was easily 5 min (2S per ultrason 3S) to form a transmant.

[0065] (3) The milky was added to 5.96 ml of 2% (W / W) PVA aqueous solution, and the magnetic...

Embodiment 2

[0068] The present invention provides a nucleic acid delivery system, named P3HB3HV3HHHX / DOTAP / siRNA nanoparticles, and the preparation method thereof is only the difference between the DOPC is replaced with an equal amount of DOTAP, and other conditions remain unchanged.

Embodiment 3

[0070] The present invention provides a nucleic acid delivery system, named P3HB3HV3HHHHX / BPEI / siRNA nanoparticles, and the preparation method thereof is only that the DOPC replaces the same amount of BPEI, and other conditions remain unchanged.

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Abstract

The invention relates to a nucleic acid delivery system as well as a preparation method and application thereof. The nucleic acid delivery system is nanoparticles formed by entrapping nucleic acid by taking polyhydroxyalkanoate and an amine material as carriers. According to the invention, the polyhydroxyalkanoate compounded amine material is creatively used as a carrier for entrapment of nucleic acid, the amine material is combined with nucleic acid molecules, and the positive electricity provided by the amine material can improve the loading efficiency of nucleic acid and improve the cellular uptake efficiency of nucleic acid; wherein the polyhydroxyalkanoate has good biodegradability and biocompatibility, and can protect the molecular stability of the nucleic acid in the delivery process, so that the nucleic acid is prevented from being degraded by nuclease and lysosome, the cellular uptake efficiency of the nucleic acid is increased, and the release time of the nucleic acid is prolonged. The finally prepared nucleic acid delivery system has good nucleic acid entrapment capacity, can effectively deliver nucleic acid drugs into cells, and has the advantages of high transfection rate and low cytotoxicity.

Description

Technical field [0001] The invention belongs to the field of biomedicine technology, and a nucleic acid delivery system and a preparation method thereof, in particular, a nucleic acid delivery system having strong package capacity, good stability, high cellular intake efficiency, and a preparation method thereof. Background technique [0002] The siRNA drug must enter the cytoplasmic and the letter to combine RNA (Messenger RNA, mRNA) to play efficacy. However, due to the large number of siRNAs and large negative charges that are easily degraded by nucleic acid enzymes, their body delivery has a large difficulty. The siRNA molecules are generally desirable to be chemically modified or packaged into a nano-carrier having a cell transfection to be taken by target cells, thereby enters the cytoplasmic to activate the RNAi mechanism. Since the molecular weight of the siRNA is large, it is loaded with negative electricity, and is susceptible to the in vivo, and the in vivo delivery of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K31/7088A61K31/713A61K47/54A61K47/59A61K48/00
CPCA61K31/713A61K31/7088A61K9/5153A61K47/595A61K47/544A61K48/0041Y02A50/30
Inventor 巫林平李玥杨明世
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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