Why are Sphingomyelin Liposomes More Popular?
Sphingomyelin is a membrane phospholipid composed of sphingosine, fatty acid, phosphoric acid and nitrogenous bases.
Among them, the fatty acyl group and the amino group are connected by an amide bond, and the formed sphingosine is also called ceramide; afterwards, phosphocholine (or phosphoethanolamine) is connected to the C-1 hydroxyl group of ceramide, and then sphingomyelin be composed.
Existing studies have shown that the synthesis of sphingomyelin involves the enzymatic transfer of phosphocholine, from phosphatidylcholine to ceramide. The first step in the synthesis of sphingomyelin is the condensation of L-serine and palmitoyl-CoA. Serine palmitoyl transferase catalyzes this reaction. The product of this reaction is reduced to produce dihydrosphingosine. dihydrosphingosine undergoes N-acylation and then desaturation to produce ceramide. Each of these reactions occurs on the cytosolic surface of the endoplasmic reticulum. Ceramide is transported to the Golgi apparatus to convert it into sphingomyelin. When phosphocholine is transferred, diacylglycerol is produced as a by-product. Degradation of sphingomyelin is responsible for many common signaling pathways. It is hydrolyzed by sphingomyelinase (sphingomyelin-specific type C phospholipase). When the ceramide diffuses through the membrane, the head group of phosphorylcholine is released into the water environment.
Because sphingomyelin (SM) is the main sphingolipid in mammalian cell membranes, and this lipid is especially rich in plasma membrane, endocytic circulatory compartment and anti-Golgi network. Therefore, it is also an important raw material in the development of drug lipid delivery systems.
Sphingomyelin Composed of Liposomes
In the process of forming liposomes, phospholipids are the basic materials of liposomes, which determine the physical and chemical properties of liposomes. The factors affecting the stability of liposome preparations include the “phase transition temperature” and “charge” related to phospholipids, the “particle size” related to the process, and the temperature, pH and ionic strength related to the environment. Among them, the type and amount of phospholipids are critical to the preparation of liposomes.
Phospholipids are classified into glycerol phosphate and sphingomyelin according to their structure. Sphingomyelin (SM) is a derivative of sphingosine. There are amide bonds in the sphingomyelin molecules, which can form hydrogen bond bands in the bimolecular membrane to stabilize the liposomes. At present, the trend of liposome products is to use sphingomyelin instead of glycerophospholipid.
There have been comparative studies on the in vitro and in vivo pharmacokinetics, tumor delivery and efficacy characteristics of liposomal vincristine preparations based on sphingomyelin (SM) and cholesterol and those composed of stearoylphosphatidylcholine (DSPC) and cholesterol Liposomes were compared. Studies have found that the in vitro stability of SM/cholesterol liposomes is significantly higher than that of similar DSPC/cholesterol liposomes. Compared with DSPC/cholesterol, SM/cholesterol liposomes also have significantly improved biological properties. Specifically, intravenous SM/cholesterol liposomes can retain 25% of the encapsulated vincristine after 72 hours of circulation, while DSPC/cholesterol liposomes only retain 5% after 72 hours of circulation. As the retention performance of SM/cholesterol liposomes is greatly improved, the vincristine level in plasma is 7 times higher than that of DSPC/cholesterol liposomes. These in turn affected the increase of vincristine accumulation in mouse ascites tumors and subcutaneous xenograft solid tumors. Eventually affect the changes in the anti-tumor efficacy of the drug. Using vincristine’s SM/cholesterol liposome formulation to treat mice with ascites tumors has a cure rate of more than 50%, while DSPC/cholesterol formulations cannot achieve this activity.This indicates that sphingomyelin exhibits superior properties when constituting liposomes. These are beneficial to follow-up drug development research.