Influence of simulated tear flow on ocular penetration of transfersomes

Transfersomes are deformable lipid vesicles extensively evaluated for transdermal drug delivery. However, the ocular penetration mechanism of transfersomes is poorly understood as the effect of tear flow, which by altering osmotic gradients across ocular tissues can influence transfersome penetration, has not been evaluated before. Hence, this study investigated the impact of simulated tear flow (STF) on the ocular distribution of curcumin-loaded transfersomes. Transfersome penetration was evaluated ex vivo under static (no STF) and dynamic (with STF) conditions and the total amount penetrated (TAP) and the maximal penetration depth (MPD) in corneal and conjunctival tissues were semi-quantitatively evaluated. Corneal distribution of transfersomes was considerably altered in the dynamic model. Drug redistribution due to STF reduced the TAP in the central cornea while increasing it in the peripheral cornea. Surprisingly, corneal MPD was significantly higher with STF, likely due to surface dehydration in the absence of STF. Meanwhile, STF reduced both TAP and MPD in the bulbar conjunctiva, although no significant difference was observed in the tarsal conjunctiva. These findings provide a mechanistic insight into ocular transfersome penetration and suggest that tear flow compromise, as observed in ocular surface disorders, may influence drug bioavailability by altering precorneal distribution and surface dehydration.