5-2.1.3.2. Negatively charged liposomes

• Generally pH-sensitive or negatively-charged liposomes are not efficient for gene transfer. They do not form a complex with it due to repulsive electrostatic interactions between the phosphate backbone of DNA and negatively charged groups of the lipids. Some of the DNA molecules get entrapped within the aqueous interior of these liposomes.
• However, formation of lipoplex, a complex between DNA and anionic lipidscan occur by using divalent cations (e.g. Ca²⁺, Mg²⁺, Mn²⁺, and Ba²⁺) which canneutralize the mutual electrostatic repulsion. These anionic lipoplexes comprise anionic lipids, divalent cations, and plasmid DNA which are physiologically safe components.
• They are termed as pH sensitive due to destabilization at low pH.

The efficiency of both in vivo and in vitrogene delivery using cationic liposomes is higher thanthat of pH sensitive liposomes. But the cationic liposomes get inactivated and unstable in the presence of serum and exhibit cytotoxicity. Due to reduced toxicity and interference from serum proteins, pH-sensitive liposomes are considered as potential gene delivery vehicles than the cationic liposomes.