DMG-PEG 2000, chemically known as 1, 2-dimyrisyl-rac-glycerol-3-methoxy polyethylene glycol 2000, is a peG-modified lipid excipient that plays a crucial role in nanomedicine delivery systems. Its CAS number is 160743-62-4, with a molecular weight of approximately 2509.2 g/mol. It usually appears as white or off-white solid powder or viscous liquid (depending on the molecular weight). This compound has good solubility and is soluble in organic solvents such as chloroform, methanol, and DMSO. It can also be dissolved in hot water. The general storage conditions are -20°C, away from light and moisture, and avoid repeated freezing and thawing.

From the perspective of molecular structure, DMG-PEG 2000 is an amphiphilic polymer, and its structure can be divided into three key parts: the hydrophilic "head", the hydrophobic "tail", and the connecting bond that links the two. The hydrophilic part is composed of methoxy-terminated polyethylene glycol (mPEG), with a molecular weight typically of 2000 Da. This hydrophilic PEG long chain is the core component that plays a role in spatial stabilization. The hydrophobic part is composed of DMG, which contains two 14-carbon DMG chains. These chains act like two "anchors" that can firmly insert into the lipid bilayer of LNP, "anchoring" the entire molecule to the surface of the nanoparticles. The hydrophilic head and hydrophobic tail are usually connected through ester bonds, which have a certain degree of hydrolyzability, meaning that they will gradually break in the in vivo environment, which is conducive to the shedding of the PEG layer and the release of drugs.

The amphiphilic structure of DMG-PEG 2000 endows it with unique self-assembly characteristics. In aqueous solutions, when the concentration reaches the critical micelle concentration (CMC), its molecules will spontaneously assemble into micelle or liposome structures. The hydrophobic tail of DMG drives the self-assembly process, while the hydrophilic chain of PEG forms a protective layer to maintain the stability of the micelles. This self-assembly characteristic is crucial for its application in drug delivery systems. The PEG hydration layer of DMG-PEG 2000 can reduce enzymatic hydrolysis and protein adsorption, and the saturated fatty acid chain of DMG endows it with high thermal stability (phase transition temperature > 50℃). However, its ester bond may hydrolyze under specific conditions, so it needs to be stored in a dry, dark place at -20°C to avoid high-temperature oxidation or repeated freeze-thaw cycles.

Compared with other pegylated lipids, DMG-PEG 2000 has unique properties. For instance, compared with DSPE-PEG 2000, DMG-PEG 2000 contains shorter acyl chains (C14 vs C18), which results in a relatively shorter residence time in the lipid bilayer. This characteristic enables DMG-PEG 2000 to dissociate relatively rapidly after LNP reaches the target site, which is conducive to drug release. It is worth noting that the in vivo half-life of DMG-PEG 2000 is usually less than 30 minutes, a characteristic that is particularly important for the release of mRNA vaccines and drugs.

From the perspective of chemical stability, the PEG chain of DMG-PEG 2000 is connected to DMG through ester bonds. These ester bonds gradually hydrolyze in the in vivo environment, leading to the shedding of the PEG layer. This controllable shedding characteristic is actually an advantage of LNP design, as it enables LNP to release the drugs it encapsulates upon reaching the target site, and also helps to reduce the PEG immune response that may occur during repeated administration. The PEG terminal of DMG-PEG 2000 is a methoxy group (-OCH₃), which is not chemically reactive but can protect the PEG chain terminal from degradation or reaction with other molecules, thereby maintaining the stability of the overall structure.

In conclusion, the chemical structure and properties of DMG-PEG 2000 make it an indispensable component in LNP delivery systems. Its ingenious amphiphilic design, appropriate hydrophobic chain length and controllable stability jointly contribute to its outstanding performance in nucleic acid drug delivery.