Lipid nanoparticle system based on corosolic acid or analogues thereof as well as preparation method and application of lipid nanoparticle system

A technology of lipid nanoparticles and corosolic acid, which is applied in the field of biomedicine and nanomedicine, can solve the problems of low targeting efficiency and intracellular delivery efficiency, and achieve the effect of improving target tissue distribution and high transfection efficiency

Pending Publication Date: 2022-04-12
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Based on the problems of low targeting efficiency and intracellular delivery efficiency in lipid nanoparticle carriers in the prior art,

Method used

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  • Lipid nanoparticle system based on corosolic acid or analogues thereof as well as preparation method and application of lipid nanoparticle system
  • Lipid nanoparticle system based on corosolic acid or analogues thereof as well as preparation method and application of lipid nanoparticle system
  • Lipid nanoparticle system based on corosolic acid or analogues thereof as well as preparation method and application of lipid nanoparticle system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Preparation of mRNA / CALNP and mRNA / LNP by Microfluidic Synthesis

[0069] Using absolute ethanol as solvent, take appropriate amount of DLin-MC3-DMA, CA or cholesterol, DMG-PEG2000 and DSPC to accurately prepare mother liquor with a concentration of 10mg / mL, and place them in a 37°C water bath to fully dissolve. Mix above-mentioned mother liquor and dehydrated alcohol in the volume shown in the table below, configure the ethanol solution of carrier material:

[0070] components DLin-MC3-DMA CA or cholesterol DMG-PEG2000 DSPC Absolute ethanol Volume / μL 177 100 21 43 659

[0071] Obtain 1 mL of ethanol solution mixed with the carrier material, and place it in a 37°C water bath to keep warm for later use.

[0072] Take 160 μg of fLucmRNA, dilute it to a total volume of 3 mL with pH=6.0 citrate buffer, and put it on ice for later use.

[0073] The NanoAssemblr microfluidic synthesis instrument and its supporting microfluidic chip were use...

Embodiment 2

[0076] Preparation of mRNA / UALNP by Microfluidic Synthesis

[0077]Using absolute ethanol as the solvent, take appropriate amount of SM-102, UA, DMG-PEG2000 and DSPC to accurately prepare mother liquor with a concentration of 10mg / mL, and place them in a 37°C water bath to fully dissolve. Mix above-mentioned mother liquor and dehydrated alcohol in the volume shown in the table below, configure the ethanol solution of carrier material:

[0078] components SM-102 UA DMG-PEG2000 DSPC Absolute ethanol Volume / μL 195 100 21 43 640

[0079] Obtain 1 mL of ethanol solution mixed with the carrier material, and place it in a 37°C water bath to keep warm for later use.

[0080] Take 160 μg of fLucmRNA, dilute it to a total volume of 3 mL with pH=6.0 citrate buffer, and put it on ice for later use.

[0081] The preparation and purification of mRNA / UALNP were the same as in Example 1. refer to figure 2 , the particle size and encapsulation efficiency ...

Embodiment 3

[0083] Preparation of mRNA / OALNP by Microfluidic Synthesis

[0084] Using absolute ethanol as solvent, take appropriate amount of ALC-0315, OA, ALC-0159 and DOPE to accurately prepare mother liquor with a concentration of 10mg / mL, and place them in a 37°C water bath to fully dissolve. Mix above-mentioned mother liquor and dehydrated alcohol in the volume shown in the table below, configure the ethanol solution of carrier material:

[0085] components ALC-0315 OA ALC-0159 DOPE Absolute ethanol Volume / μL 211 100 20 41 628

[0086] Obtain 1 mL of ethanol solution mixed with the carrier material, and place it in a 37°C water bath to keep warm for later use.

[0087] Take 160 μg of fLucmRNA, dilute it to a total volume of 3 mL with pH=6.0 citrate buffer, and put it on ice for later use.

[0088] The preparation and purification of mRNA / OALNP were the same as in Example 1. refer to figure 2 , the particle size and encapsulation efficiency of th...

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Abstract

The invention relates to a lipid nanoparticle system based on corosolic acid or analogues thereof as well as a preparation method and application of the lipid nanoparticle system. The lipid nanoparticles provided by the invention are prepared from corosolic acid or analogues thereof and a lipid material, the corosolic acid analogues comprise ursolic acid and oleanolic acid, and the lipid material consists of ionizable cationic lipid, neutral phospholipid, PEGylated phospholipid and cholesterol-containing or cholesterol-free materials. The molar ratio of corosolic acid or analogues thereof to the liposome material is (1: 9)-(1: 1). Compared with the prior art, the lipid nanoparticles based on corosolic acid or analogues thereof provided by the invention have stronger cell transmembrane and tissue infiltration capacities, are used as delivery carriers of nucleic acid molecules, can be efficiently taken by cells after entrapment of at least one nucleic acid drug, and can be effectively absorbed by the cells through endosome escape capacity. The prevention and treatment effects of the nucleic acid medicines are obviously improved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and nanomedicine, and in particular relates to a lipid nanoparticle system based on corosolic acid or its analogues and its preparation method and application. Background technique [0002] Nucleic acid drugs mainly refer to nucleotide or deoxynucleotide-containing compounds with genetic characteristics and pharmacological activity, mainly including small interfering RNA (small interfering RNA, siRNA), messenger RNA (Messenger RNA, mRNA, plasmid DNA, etc. RNA is Genetic information present in biological cells, some viruses and viroids. siRNA is an artificially synthesized double-stranded RNA, which is the main member of the RNA-induced silencing complex, which stimulates the silencing of the complementary target messenger RNA and blocks the translation of mRNA and protein expression. mRNA is a transient intermediate between gene and protein, which is transcribed from one strand of DNA and is t...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K31/713A61K47/28A61P3/10A61P31/00A61P35/00B82Y5/00B82Y40/00
Inventor 姜嫣嫣刘云虎杨月滢
Owner FUDAN UNIV
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