Cationic liposome

Cationic liposomes are spherical structures that contain positively charged lipids. Cationic liposomes can vary in size between 40 nm and 500 nm, and they can either have one lipid bilayer (monolamellar) or multiple lipid bilayers (multilamellar). The positive charge of the phospholipids allows cationic liposomes to form complexes with negatively charged nucleic acids (DNA, mRNA, and siRNA) through ionic interactions. Upon interacting with nucleic acids, cationic liposomes form clusters of aggregated vesicles. These interactions allow cationic liposomes to condense and encapsulate various therapeutic and diagnostic agents in their aqueous compartment or in their lipid bilayer. These cationic liposome nucleic acid complexes are also referred to as lipoplexes. Due to the overall positive charge of cationic liposomes, they interact with negatively charged cell membranes more readily than classic liposomes. These issues can be reduced by optimizing the physical and chemical properties of cationic liposomes through their lipid composition. The first formulations were designed using all natural lipids. based on his research into cationic lipids at Syntex from 1982 to 1988. Felgner introduced the first cationic lipid used for gene delivery, N [1 (2,3 dioleyloxy)propyl] N,N,N trimethylammonium chloride (DOTMA).

The use of cationic lipids helps to enhance the overall stability and efficiency of liposomes. Although cationic lipids themselves are able to encapsulate nucleic acids into liposomes, the transfection efficiency is low due to a process known as endosomal escape. Lipids that are capable of destabilizing endosomal membranes and facilitating endosomal escape are known as fusogenic lipids. The addition of helper lipids to the cationic lipids demonstrates a much higher transfection efficiency.

Cationic liposomes can deliver nucleic acids into the cell through an endocytotic pathway or through cell membrane fusion. Fusogenic cationic liposomes almost exclusively deliver nucleic acids through cell membrane fusion. Cationic liposomes in the lamellar phase deliver nucleic acids through endocytosis, specifically clathrin mediated endocytosis (CME), caveolae mediated endocytosis (CavME), and macropinocytosis.

Paclitaxel (PTX) is a chemotherapy medication used to treat many types of cancer, such as ovarian cancer, breast cancer, and pancreatic cancer. SynCore Bio's EndoTAG 1 is a cationic liposome formulation with embedded PTX. The cationic lipid used in this formulation is dioleoyloxypropyltrimethylammonium (DOTAP). The PTX embedded cationic liposome interacts with the negatively charged tumor endothelial cells required for tumor angiogenesis, in order to reduce their tumor blood supply.

The positive charge of cationic lipids has been shown to have cytotoxic effects, as these lipids can activate several pro apoptotic and pro inflammatory cell signaling pathways. Due to their positive charge, cationic liposomes bind to various plasma proteins, forming a protein corona on their surface and completely changing their biological identity. This new biological identity then causes opsonins to tag them as pathogens and encourages clearance through phagocytic clearance.