Lipoid-cation polymer and preparation method thereof

A cationic polymer and lipid technology, which is applied in the field of lipid-cationic polymer and its preparation, can solve the problems of toxic reaction and low gene transfection efficiency, achieve good stability, enhance gene transfection efficiency, and is not easy to Gathering effect

Inactive Publication Date: 2012-07-11
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, cationic polymers are mostly non-biodegradable materials, especially after repeated administration, these materials will accumulate in the body and may cause toxic reactions, and the gene transfection efficiency is relatively low

Method used

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  • Lipoid-cation polymer and preparation method thereof
  • Lipoid-cation polymer and preparation method thereof
  • Lipoid-cation polymer and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1 prepares lipid-cationic polymer

[0034] The method is:

[0035] (1) Weigh 10mg DOPE-GA and dissolve it in 6ml anhydrous DMF, add 5mg NHS and 8mg DCC, and react at 40°C for 24h.

[0036] (2) Weigh 50 mg of PEG-b-PLL, dissolve it in 3 ml of DMF, and add it dropwise to the above reaction system. After reacting for 72 hours, cool the reaction solution in an ice bath for 4 hours, and filter to remove the white precipitate.

[0037] (3) Dialyze the filtrate in a Mw8000-14000 dialysis bag for 48 hours, filter, and freeze-dry the filtrate to obtain the lipid-cationic polymer DOPE-g-PLL-b-PEG.

[0038] The preparation method of described PEG-b-PLL is as follows: (other embodiments are with embodiment 1)

[0039] H 2 N-PEG and ε-benzyloxycarbonyl-L-lysine-N-carboxylic acid anhydride (Lys(z)-NCA) were dissolved in DMF, fed with dry argon, stirred, and reacted at 30°C for 72h. The reaction solution was dropped into excess anhydrous ether, and centrifuged to obtain...

Embodiment 2

[0042] Embodiment 2 prepares lipid-cationic polymer

[0043] The method is:

[0044] (1) Weigh 50mg of DOPE-GA and dissolve it in 10ml of anhydrous DMF, react with 30mg of NHS and 40mg of DCC at 40°C for 12h.

[0045] (2) Weigh 300 mg of PEG-b-PLL, dissolve it in 10 ml of DMF, then add it dropwise to the above reaction system, react for 96 hours, cool the reaction solution in an ice bath for 5 hours, and filter to remove the white precipitate.

[0046] (3) Dialyze the filtrate in a Mw8000-14000 dialysis bag for 48 hours, filter, and freeze-dry the filtrate to obtain the lipid-cationic polymer DOPE-g-PLL-b-PEG.

Embodiment 3

[0047] Embodiment 3 prepares lipid-cationic polymer

[0048] The method is:

[0049] (1) Weigh 40mg of DPPE-GA and dissolve it in 10ml of anhydrous DMF, add 20mg of NHS and 20mg of DCC, and react at 30°C for 24h.

[0050] (2) Weigh 100mg of PEG-b-PLL, dissolve it in 5ml of DMF, then add it dropwise to the above reaction system, react for 48h, cool the reaction solution in an ice bath for 2h, and filter to remove the white precipitate.

[0051] (3) Dialyze the filtrate in a Mw8000-14000 dialysis bag for 48 hours, filter, and freeze-dry the filtrate to obtain the lipid-cationic polymer DPPE-g-PLL-b-PEG.

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Abstract

The invention discloses a lipoid-cation polymer with a structural formula shown in the specification, wherein in the structural formula, m and n are both positive integers, m is any integer from 60 to 120 and n is any integer from 80 to 250. The lipoid-cation polymer can be used as a carrier for carrying nucleic acid, and in a gene therapy, the lipoid-cation polymer is combined with the nucleic acid to prepare a gene-borne nano composite to be introduced into a cell. The gene-borne nano composite synthesized in the invention is prepared by utilizing residual amino groups on a lipoid-cation polymer skeleton and DNA or RNA to spontaneously form a polyion polymer micelle, the DNA or RNA and the polycations form an inner core cladded with a lipid material, and a hydrophilic polymer PEG (Polyethylene Glycol) is enveloped on the outer layer. The core-shell structure enables the gene-borne nano composite to have high colloid stability and can reduce the interaction between the nano compositeand a blood plasma component.

Description

technical field [0001] The invention relates to a lipid-cationic polymer and a preparation method thereof. Background technique [0002] Gene therapy is to introduce the target gene into the patient's specific tissue cells (target cells) for proper expression through an appropriate carrier, so as to correct or compensate the diseases caused by gene defects and abnormalities, so as to achieve the purpose of treatment. However, DNA transfection efficiency is usually low and gene expression is short-lived, the ability to penetrate cells is weak, it is difficult to effectively transfer into the nucleus, and the number and proportion of tumor cells that can be transduced by plasmids is small. In addition, it is easily cleared by tissues and difficult to transport throughout the body. Therefore, it is necessary for the gene carrier to carry the gene into the target cell and reduce the probability of its degradation, so as to improve the efficiency of gene expression. [0003] Ge...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G69/48C08G65/48C12N15/63A61K48/00A61K47/34
Inventor 张娜孙晓利刘春喜李鹏刘永军
Owner SHANDONG UNIV
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