Delivery of ophthalmic drugs to the interior parts of the eye for effective treatment of glaucoma (i.e., a chronic disease) remains a huge challenge because of the well-known static and dynamic ocular barriers. Herein, we present a new antiglaucoma formulation based on the development of a dual-functional therapeutic nanocarrier platform for intraocular targeted and sustained delivery of pilocarpine. Specifically, chitosan and ZM241385 are functionalized onto surfaces of hollow ceria nanoparticles (hCe NPs), thereby endowing the nanocarriers with a strong capability to open corneal epithelial tight junctions and deliver drug molecules to the targeted intraocular tissue (i.e., ciliary body). Moreover, the nanocarriers are demonstrated in vitro and in vivo to possess potent anti-oxidant and anti-inflammatory properties, which are beneficial to simultaneously alleviate glaucomatous damage. Single topical instillation of the pilocarpine-loaded dual-functional therapeutic nanocarriers with optimized delivery performance onto experimentally glaucomatous eyes can effectively mitigate disease progression for 7 days while that employing the traditional commercial eye drops only provides a moderate treatment efficacy for 4 h, possibly due to improved intraocular drug delivery (∼250-fold greater bioavailability in the ciliary body) and intrinsic therapeutic activity of the ophthalmic formulation. These findings show great promise for the development of advanced nano eye drops toward efficient management of ocular diseases occurred in the inner segments of the eye.

由于众所周知的静态和动态眼屏障，将眼科药物递送到眼睛的内部以有效治疗青光眼（即，慢性疾病）仍然是巨大的挑战。在本文中，我们基于双功能治疗纳米载体平台的发展，为眼球靶向和持续递送毛果芸香碱提供了一种新的抗青光眼制剂。具体而言，将壳聚糖和ZM241385功能化在空心二氧化铈纳米颗粒（hCe NPs）的表面上，从而赋予纳米载体强大的能力，以打开角膜上皮紧密连接并将药物分子递送至目标眼内组织（即睫状体）。此外，纳米载体已在体外和体内得到证实具有有效的抗氧化和抗炎特性，有利于同时减轻青光眼的损害。将具有优化的递送性能的毛果芸香碱负载的双功能治疗性纳米载体单次滴注到实验性青光眼上可以有效缓解疾病进展7天，而使用传统的商业滴眼液只能提供4 h的中等治疗效果，可能是由于改善了眼内药物的递送（在睫状体中的生物利用度提高了约250倍）和眼科制剂的内在治疗活性。这些发现表明，开发先进的纳米滴眼液有望有效治疗眼内部分发生的眼部疾病。