Amphiphilic triblock copolymer, preparation method and siRNA drug carrier

A hydrophilic polymer and polymer technology, applied in the field of life medicine, can solve the problems of low transfection efficiency, immune stimulation, toxicity, etc., and achieve the effect of high repeatability, good biocompatibility, and good stability

Inactive Publication Date: 2014-04-23
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although some breakthroughs and developments have been made in the research of siRNA drug delivery carriers, there are still some key issues to be solved before siRNA drugs can be successfully used in the treatment of human diseases, such as toxicity, specificity, targeting, and immune stimulation. , low transfection efficiency, etc.

Method used

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  • Amphiphilic triblock copolymer, preparation method and siRNA drug carrier
  • Amphiphilic triblock copolymer, preparation method and siRNA drug carrier
  • Amphiphilic triblock copolymer, preparation method and siRNA drug carrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Embodiment 1, the synthesis and characterization of prepolymer mA-B-acrylated and mB-A-acrylated

[0063] 1. Synthesis and characterization of propylene-terminated polyhydroxyalkanoate monomethyl ether-polyethylene glycol (mA-B-acrylated)

[0064] (1) Synthesis and characterization of mono / dihydroxy polyhydroxyalkanoate (mPHA-OH / PHA-diol)

[0065] The synthesis of various mono / dihydroxy polyhydroxyalkanoate (mPHA-OH / PHA-diol) is prepared by transesterification reaction with methanol or diol under the catalysis of p-toluenesulfonic acid (PTSA). The alcohol may be ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol. All kinds of polyhydroxyalkanoate raw materials in the present invention are purchased from Shenzhen Ecoman Biotechnology Co., Ltd. The diol (P3 / 4HB-diol ) as an example to illustrate the operation steps of this type of reaction.

[0066] The synthetic route of mP3 / 4HB-OH is as follows figure 1 (A) shown. mP3 / 4HB-OH is prepared by transeste...

Embodiment 2

[0092] Embodiment 2, the synthesis and characterization of formula I compound mA-B-C or mB-A-C

[0093] Various types of mA-B-C or mB-A-C copolymers with different molecular weights are made of mA-B-acrylated or mB-A-acrylated with corresponding types and corresponding molecular weights as prepolymers, and react with amino groups of cationic compounds through Michael addition .

[0094] Synthesis schematic as figure 1 As shown in (D): react the terminal acryl group of the prepolymer mA-B-acrylate or mB-A-acrylate with the amino group of the cationic compound under certain conditions to obtain the compound of formula I.

[0095] Using mP3 / 4HB-PEG-acrylate or mPEG-P3 / 4HB-acrylate with cationic polymer lPEI (which has a weight average molecular weight ranging from 600 to 22,000 Daltons, those skilled in the art can according to specific needs, in practice Specific selection in the application) to prepare mP3 / 4HB-PEG-lPEI or mPEG-P3 / 4HB-lPEI copolymer as an example to illustrat...

Embodiment 3

[0105] Embodiment 3, prepare nanoparticle with formula I compound mA-B-C or mB-A-C

[0106] 1. Preparation of nanoparticles

[0107] Amphiphilic triblock copolymers have hydrophobic and hydrophilic interactions in aqueous solution, and nanoparticles can be formed as long as the copolymer concentration is higher than the critical micelle concentration. All kinds of compounds of formula I prepared in the present invention are composed of cationic compound of hydrophilic part, hydrophilic polymer and polyhydroxyalkanoate of hydrophobic part, so they can self-assemble to form nanoparticles in aqueous solution. The following takes the preparation of nanoparticle of material 1 as an example to illustrate the preparation method of various compound nanoparticles of formula I in the present invention.

[0108] There are many ways to prepare nanoparticles, the most common one is the solvent evaporation method. The specific method is: dissolve 20mg of material 1 in 2ml of tetrahydrofura...

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Abstract

The invention discloses an amphiphilic triblock copolymer and a preparation method, the amphiphilic triblock copolymer is a polymer formed by copolymerization of polyhydroxyalkanoate, a hydrophilic polymer and a cationic polymer, a structural general formula is [mA-B-C] or [mB-A-C], wherein A is from polyhydroxyalkanoate, mA represents monomethyl ether of polyhydroxyalkanoate, B is from the hydrophilic polymer, mB represents monomethyl ether of hydrophilic polymer, C is from a cationic compound , the cationic compound comprises cationic peptide, cationic ester and the cationic polymer. The invention also discloses a siRNA drug delivery, its active component is nano particles with positive charge of amphiphilic triblock copolymer, the particle size of the nano particles is between 50 and 400nm, and its zeta potential is 5-60mV. The polymer has the characteristics of biocompatibility and relative hydrophobicity; the formed nano particles have good stability, the preparation method is simple, the repeatability is high, the raw material is cheap and the cost can be saved.

Description

technical field [0001] The invention relates to an amphiphilic triblock polymer based on polyhydroxyalkanoate, a preparation method thereof and an siRNA drug carrier, belonging to the field of life medicine. Background technique [0002] RNA interference is a sequence-specific, post-transcriptional gene silencing technology mediated by double-stranded small interfering RNA (siRNA) consisting of 21-23 nucleotides. Because RNA interference technology can efficiently and specifically silence disease-related genes, it has gradually been developed into a new gene therapy method for the treatment of hereditary or acquired diseases, including viral infections and cancers. So far, a large number of siRNAs have been used. Carry out animal experiments and clinical experiments for disease treatment. These mainly include viral experiments against hepatitis B and C viruses, HIV, etc., research related to neurodegenerative diseases, and cancer treatments that target genes that express ge...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00C08G81/00C08G63/91C08G65/48A61K47/48A61K47/34A61K47/59
Inventor 张必良周丽
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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