Bhujbal Santosh, Rupenthal Ilva D, Agarwal Priyanka
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, Aotearoa-New Zealand National Eye Centre, The University of Auckland, Auckland, 1142, New Zealand.
Drug Deliv Transl Res. 2025 May 13. doi: 10.1007/s13346-025-01872-2.
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 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 was 6-fold greater with TFS. Interestingly, despite simulated tear flow, the T 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.
虽然传递体（TFS）作为皮肤局部给药载体已得到广泛研究，但其在眼部给药中的应用仍 largely 未被探索。本研究旨在使用离体模型评估载有托纳贝萨特的 TFS 的耐受性、接触角和眼部渗透性，重点是比较药物在不同眼组织中的分布。将托纳贝萨特在中链甘油三酯（MCT）中的溶液用作对照。使用鸡胚绒毛尿囊膜上的 Hen 氏鸡蛋试验（HET-CAM）评估结膜耐受性，而使用牛角膜混浊和通透性（BCOP）试验来确定角膜耐受性。使用测角仪测量新鲜切除的牛角膜上的滴眼接触角。在滴眼后 0.25、0.5、1 和 2 小时，使用离体猪全眼模型在模拟泪液流动下评估药物向角膜、结膜、眼睑和巩膜 - 脉络膜的渗透。TFS 和 MCT 制剂均表现出良好的结膜和角膜耐受性，TFS 在角膜表面的接触角低于 MCT。使用 TFS 滴眼剂在所有眼组织中均达到了显著更高的药物浓度，TFS 的 C 在结膜、眼睑和巩膜 - 脉络膜中至少比 MCT 溶液高 16 倍，在后者中差异最大。同时，TFS 的角膜 C 高 6 倍。有趣的是，尽管有模拟泪液流动，但在所有眼组织中 TFS 的 T 在较晚时间点被观察到。总体而言，本研究表明 TFS 在眼表面耐受性良好，具有向眼组织持续和靶向给药的潜力。因此，它们为安全有效的眼部给药提供了一种有前景的替代方法。
