New insights on liposomal formulations based upon tear film lipids: A combined study of safety and ocular surface pharmacokinetics.

Abstract

Dry Eye Disease (DED) is a chronic disorder originating from the loss of tear film homeostasis and associated with ocular surface damage, irritation, pain, and blurred vision. There is a need for new treatments of DED and strategies based on enhancing the function of the tear film lipid layer have shown significant promise. In this study, our aim was to develop liposomal formulations based on central tear film lipid species such as a phosphatidylcholine (PC), a wax ester (WE) and an O-acyl-ω-hydroxy fatty acid (OAHFA). In more detail, two liposomal formulations were developed and characterized by physicochemical techniques in vitro followed by cytotoxicity studies in vitro (human corneal epithelial; HCE cells) and tolerability studies in vivo (rats and rabbits). To obtain more insights of the potential functionality of the formulations, their ability to promote the recovery of damaged HCE cells was assessed in vitro, the residence time of WE and OAHFA from rabbit tear fluid was determined in vivo, and the permeation and distribution of these lipids in excised rabbit cornea was investigated ex vivo. Both formulations were considered well-tolerated in vitro and in vivo, and possessed acceptable features for ocular administration. Also, in vitro cell recovery studies showed promise. No considerable differences were observed between the formulations in terms of the residence time of the WE and OAHFA utilized. Moreover, the studies indicated that these lipid species may accumulate in the corneal epithelium and thereafter distribute back to the tear fluid (especially in the case of the OAHFAs) after a longer dosing period. However, this topic requires further investigation in the future. Altogether, important new insights on the biocompatibility and performance of tear film lipid based formulations were uncovered through this work.