Nonlamellar Phases in Cationic Phospholipids, Relevance to Drug and Gene Delivery

Lipid aggregates have been used as drug carriers for several decades. Recently, nonlamellar liquid crystalline lipid systems have attracted attention as possible drug-delivery vehicles because of their unique nanostructure and physicochemical properties. Here we summarize data on the nonlamellar phase-forming propensity of the cationic phosphatidylcholines (cationic PCs). The class of cationic PCs has been specifically designed and explored for the purpose of nonviral gene delivery. These lipids were found to comprise an attractive cationic lipid class because they are biodegradable, have low toxicities, and in a number of cases, display high transfection activity. Lipids of this class form a variety of polymorphic and mesomorphic phases-lamellar and nonlamellar, depending on the structure of their hydrocarbon chains and especially on the third hydrocarbon chain used to alkylate the PC phosphate group and convert the zwitterionic PC headgroup into a cation. Here we characterize the phase behavior and transfection activity of eight cationic PCs that have been identified as forming nonlamellar phases-inverted hexagonal and cubic. We then demonstrate that those cationic PCs that also form nonlamellar lipoplexes are notably less efficient gene nanocarriers in comparison with the cationic PCs forming lamellar phase lipoplexes.