National Engineering Research Center of Ophthalmology and Optometry, School of Ophthalmology and Optometry & Biomedical Engineering, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
National Engineering Research Center of Ophthalmology and Optometry, School of Ophthalmology and Optometry & Biomedical Engineering, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
Int J Pharm. 2024 Sep 30;663:124563. doi: 10.1016/j.ijpharm.2024.124563. Epub 2024 Aug 5.
The modulation of inflammation is effective to treat many ocular surface diseases. Thus the low bioavailability of common anti-inflammatory eye-drops urges the development of ocular drug delivery systems to extend the ocular retention and enhance the cellular uptake for improving anti-inflammatory effect of eye-drops. Here we covalently conjugate two molecules of clinically anti-inflammatory drug (i.e., dexamethasone) with a small peptide (i.e., Tyr-Glu-Asn-Pro-Thr-Tyr) to generate an anti-inflammatory hydrogel eye-drop. With a self-assembled ability, the designed supramolecular hydrogel achieves gel-sol-gel transition by varying shearing forces which increases the pre-corneal retention of drug. The fluorescent imaging reveals the efficient cellular uptake of designed conjugate via clathrin-mediated endocytosis. A rodent model of endotoxin-induced uveitis verifies that the supramolecular hydrogel eye-drop suppresses inflammation responses without ocular irritation. As a rational approach to design anti-inflammatory drugs as eye-drops, this work overcomes the frequent instillation of clinical eye-drops and further improves the bioavailability of anti-inflammatory drugs, which may provide an effective and household way to fight ocular surface inflammation.
炎症调节对于治疗多种眼表疾病非常有效。因此，常见抗炎眼药水的生物利用度较低，促使人们开发眼用药物传递系统，以延长眼部滞留时间并增强细胞摄取，从而提高眼药水的抗炎效果。在这里，我们将两种临床抗炎药物（即地塞米松）与一种小肽（即 Tyr-Glu-Asn-Pro-Thr-Tyr）共价连接，生成一种抗炎水凝胶眼药水。通过自组装能力，设计的超分子水凝胶通过改变剪切力实现凝胶-溶胶-凝胶转变，从而增加药物在角膜前的滞留时间。荧光成像显示，设计的缀合物通过网格蛋白介导的内吞作用实现了有效的细胞摄取。内毒素诱导的葡萄膜炎啮齿动物模型验证了超分子水凝胶眼药水能够抑制炎症反应而不引起眼部刺激。作为一种设计抗炎药物作为眼药水的合理方法，该工作克服了临床眼药水频繁滴眼的问题，并进一步提高了抗炎药物的生物利用度，为对抗眼表炎症提供了一种有效且便捷的方法。
