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Cationic phospholipid PEG2000-C-DMG applied to the famous siRNA liposome Onpattro

Time:2020-07-17

Views:821

Speaking of Onpattro, as the first siRNA liposome already on the market, its reputation is not small. Previously, AVT editor mentioned the prescription of siRNA liposome Onpattro when introducing DLin-MC3-DMA, in addition to DLin-MC3-DMA There is also a new face PEG2000-C-DMG. It is also a cationic lipid. What effect does the cationic phospholipid PEG2000-C-DMG play in siRNA liposome Onpattro? Is there any connection and difference with the familiar DSPE-PEG2000?


Cationic phospholipid PEG2000-C-DMG applied to the famous siRNA liposome Onpattro-AVT (Shanghai) Pharmaceutical Tech Co., Ltd.


The role of PEG2000-C-DMG in the prescription is to prevent aggregation between particles, and the second is to use PEG2000's "invisible" effect to achieve long circulation and passive targeting. So why not use DSPE-PEG2000 but work hard to develop a new accessory? According to the research of the original research company Alnylam, the type and number of PEGylated lipids used in the prescription not only determine the size of the liposome, but also strongly affect the gene silencing ability. Obviously DSPE is not as good as C-DMA at this point Have any advantage. PEG2000-C-DMG can reduce the interaction between liposomes and cells and the ability to adsorb ApoE. At the same time, the use of polyethylene glycol lipids containing short acyl chains (C14 M) can achieve rapid escape while in vivo Dissociation, the half-life in vivo is less than 30min, and the best hepatocyte gene silencing effect is obtained. The dosage of PEG2000-C-DMG in Onpattro is as follows:


Cationic phospholipid PEG2000-C-DMG applied to the famous siRNA liposome Onpattro-AVT (Shanghai) Pharmaceutical Tech Co., Ltd.


According to my own analysis, PEG2000-C-DMG can also be used in the preparation of cationic liposomes for small molecule anticancer drugs, replacing DSPE-PEG2000. In the weakly acidic tumor microenvironment, the PEG2000-C-DMA amide bond breaks to form a trivalent quaternary ammonium salt, which exposes a positive charge, which makes the particles more positively charged, that is, more cytotoxic, and has a more obvious killing effect on tumor neovascularization.However, this reaction is not likely to occur under normal physiological conditions, so the prepared cationic liposomes have pH sensitivity, higher safety and better tumor suppressing effect.

There is not much knowledge about the new member of the lipid family PEG2000-C-DMG. If you have good opinions and research results, please share them and exchange learning with your friends.

For more information about cationic lipids, stay tuned to AVT (Shanghai) Pharmaceutical Tech Co., Ltd.!

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