Measurement and Control of the Size Distribution of Electrospray Generated Liposomes for Gene Delivery

Manufacture of liposome nanoparticles is an important step in the delivery of gene therapeutics for treatment of cancer. It is advantageous to be able to control the size and morphology of such liposomes. In this work, the process parameters of electrohydrodynamic spray (electrospray) are systematically investigated to determine their effect on liposome size. A co-axial electrospray set up is used to generate liposomes. Hydrodynamic diameter is measured using light scattering techniques. The parameters investigated include solvent effects, charge interaction, lipid concentration flow configuration and flow rate. Solvent polarity influences the mixing of the lipid and aqeuous phases affecting the size. Evaporation rate only affects liposome size in the inverted jet geometry. Lipid concentration and flow rate are both be tuned to optimize particle size. Including negatively charged oligodeoxynucleotides increases particle size. Conditions are shown which generate liposome encapsulated ODN by electrospray with a particle size of 109 nm.