In vivo fate of liposomes after subconjunctival ocular delivery

Subconjunctival administration of nanocarriers presents an alternative drug delivery strategy to overcome blood-ocular barriers to enhance drug bioavailability to specific parts of the eye. Using fiberoptic Confocal Laser Microendoscopy (CLM) and radiotracing, we describe the effects of charge, size, cholesterol content and lipid saturation on the ocular and corporal distribution of liposome nanocarriers in live mouse models. Positively charged or large (>250 nm) liposomes exhibit sustained ocular residence times in and around the injection site; cholesterol loading slows down this clearance, whereas lipid saturation accelerates clearance. Neutral, negatively charged, or smaller sized liposomes distribute to the limbus, rich in stem cells and blood capillaries. Differential lymphatic and systemic clearance from the eye to corporeal tissues was also observed across formulations. These results demonstrate the need to optimize liposome design for control over temporal and spatial nanocarrier bioavailability and clearance from the eye for improved efficacy and safety of ocular therapeutics.