Application of Cationic liposome DMG-PEG2000 in RNA drug liposomes

Dmg-peg2000 in the square of the role of one is to prevent the aggregation of particles, the second is to use PEG2000 "invisible" effect to achieve long cycle and passive targeting. So why not use DSPE-PEG2000 instead of trying to develop a new accessory? According to the original research company Alnylam's research, the type and number of peg-lipids used by Chu Square not only determine the size of the liposome particle size, but also strongly affect the gene silencing ability, obviously DSPE in this point compared with DMG-PEG2000 does not have any advantage.


Dmg-peg2000 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 chain (C14 M), can achieve in vivo escape and rapid dissociation, in vivo half-life <30min, to obtain the best liver cell gene silencing effect.

Dmg-peg2000 in English, 1, 2-dimyristoyl-RAC-glycero-3-methoxypolyethylene glycol-2000, Chinese name can be translated as dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000.

Its molecular formula is C122H242O50, its molecular weight is 2509.2 (average), and its structure is as follows:
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From the structural equation, it can be seen that this material is modified by pegging a short-chain lipid, C14 chain is much shorter than the common DSPE-MPEG2000 C18 chain, so the direct result is that the lipid "anchor" inserted into the lipid membrane is "shallow", easier to fall off in the process of systemic circulation. The advantage of this design is that it solves the PEG-Dilemma.

There are three main aspects of PEG-Dilemma:

1. The steric hindrance of PEG chain shields the interaction between liposome and cell membrane, and yi makes the uptake of liposome by target cells;
2. Shielding the interaction between liposomes and endosomal membrane prevents "endosomal escape", resulting in RNA degradation and unable to enter the cytoplasm;
3. Multiple injections of PEGylated liposomes induce immune response and cause accelerated blood qingchu (ABC) phenomenon.

General solutions include: reducing the density of PEG on the liposome surface; Break peG-lipid linkers such as ester, hydrazone, and peptide bonds; The use of short chain lipids, such as C14 lipids, is easier to dissociate PEG from the particle surface than C18 lipids.

In addition, dmG-PEG2000's short chain (myrodamic acid, C14) can degrade faster than the long chain (stearic acid, C18) with a small half-life. Dmg-peg2000 can reduce the interaction between liposomes and cells and the ability to adsorb ApoE, and obtain good cell gene silencing effect.

Lysosome/endosomal escape is the key and difficult part of RNA drug delivery, and its efficacy is directly related to it. The use of polyethylene glycol lipids containing short alkyl chains can achieve rapid dissociation while escaping from the body, so as to combat the failure of "endosomal escape" caused by PEG.

This is why DSPE-MPEG2000 is commonly used in chemical liposomes and nucleic acid liposome drugs using DMG-PEG2000 have higher gene silencing/expression level and good efficacy.

With this in mind, many new peg-lipids such as DMA-PEG2000 and PEG2000-Ceramide-C14 have been developed for use in scientific research.