Development, characterization and pulmonary disposition of liposomal ciprofloxacin formulations

Abstract

The objective of this research was to develop and characterize novel liposomal ciprofloxacin formulations with modified release profiles, providing both faster and slower release of drug compared to the traditional liposomal formulation. The challenge was to do this without utilizing new lipid compositions, but instead by developing simple procedures to alter specific features of the liposomes. The new formulations were characterized by cryo-TEM analysis, dynamic light scattering, in vitro release assay, aerosol particle size distribution and the effect of mesh nebulization on functionality. A liposomal ciprofloxacin formulation was modified in two ways: 1. by addition of surfactant (e.g., 0.2% polysorbate 80 or 0.4% polysorbate 20) after osmotic swelling in a hypotonic environment to create a more permeable membrane which resulted in significantly faster release properties, and 2. by freeze-thaw to transform the drug into a nanocrystalline state inside the liposome to create a slower releasing formulation. For both situations, the liposomes maintained their vesicular structure. These experiments demonstrate two simple but novel ways to modify the encapsulation state and release properties of a liposome formulation. These examples demonstrate the potential to develop personalized therapies for patients by dialing-in the appropriate release properties of a liposomal drug product based on patient-based metrics.