Evaluation of ocular tolerability and bioavailability of tonabersat transfersomes ex vivo

While transfersomes (TFS) have extensively been investigated as carriers for topical drug delivery to the skin, their application in ocular drug delivery remains largely unexplored. This study aimed to evaluate the tolerability, contact angle, and ocular penetration of tonabersat-loaded TFS using ex vivo models, with a focus on comparing drug distribution in different ocular tissues. A solution of tonabersat in medium chain triglycerides (MCT) was used as the control. Conjunctival tolerability was evaluated using the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM), while the Bovine Corneal Opacity and Permeability (BCOP) assay was used to establish corneal tolerability. Drop contact angle on freshly excised bovine corneas was measured using a goniometer. Drug penetration into the cornea, conjunctiva, eyelid and sclera-choroid was evaluated using an ex vivo porcine whole eye model under simulated tear flow, 0.25, 0.5, 1, and 2 h after eyedrop application. Both the TFS and MCT formulations exhibited good conjunctival and corneal tolerability with the TFS contact angle on the corneal surface being lower than that of MCT. Significantly greater drug concentrations were achieved in all ocular tissues with the TFS eyedrop, with the C_max from TFS being at least 16-fold higher than that achieved with the MCT solution in the conjunctiva, eyelid and sclera-choroid, with the difference being greatest in the latter. Meanwhile, the corneal C_max was 6-fold greater with TFS. Interestingly, despite simulated tear flow, the T_max was observed at a later timepoint with TFS in all ocular tissues. Overall, this study demonstrates that TFS are well tolerated on the ocular surface and have the potential for sustained and targeted drug delivery to ocular tissues. Thus, they present a promising alternative for safe and effective ocular drug delivery.

Bioavailability; Ocular drug delivery; Penetration; Tolerability; Tonabersat; Transfersomes.