Real time monitoring of lipoplex molar mass, size and density.

Time-resolved multiangle laser light scattering (TR-MALLS) is used to monitor the temporal variation of DNA/cationic liposome lipoplex molar masses and geometric sizes throughout the complexation process. The measured molar masses and geometric sizes are in turn used to estimate lipoplex density. The DNA/cationic lipid charge ratio is found to be the primary factor governing lipoplex formation kinetics and the final lipoplex molar mass, geometric size and density. Charge ratios near unity lead to a growing kinetic regime in which initially formed primary lipoplexes undergo further aggregation eventually forming large molar mass lipoplexes of high density, while charge ratios very far from unity yield low molar mass lipoplexes of lower density. It is also noted that solvent composition can play a significant role in the lipoplex formation process with lipoplexes formed in ion-containing media being larger and denser than those formed in dextrose solution.