Abstract

Contact lenses are ideally suited for sustained ocular drug delivery to bypass the issues associated with eye drop therapy. However, drugs such as bimatoprost loaded by the conventional soaking method show poor drug uptake, high burst release, and altered critical lens properties. In this study, the effect of gold nanoparticles (GNPs) on bimatoprost loading/uptake from the soaking solution and its release kinetics from the lens was investigated. In one method, GNP solutions of varying strength were loaded into the bimatoprost soaking solution (mM-SS batches), and in another method, the GNPs were included in the contact lens matrix during casting (mM-GN-L batches). The GNPs were spherical with average size of 21.1 nm and −20.1 mV zeta potential. The swelling, oxygen permeability, and optical transmittance of the lens were improved compared to those of the lens drug-loaded by the conventional soaking method (SM-L). The mM-GN-L batches showed significant improvement in drug uptake from the soaking solution compared to the SM-L and mM-SS batches. The in vitro studies showed relatively low burst and sustained bimatoprost release up to 72 h compared to 24 h with the SM-L batch. The ability to sustain drug release improved proportionally with an increase in the amount of GNPs in the lens. The presence of GNPs lowered protein adherence. The GNP-laden lenses were deemed safe in ocular irritation and histopathology reports (rabbit model). Further, they showed higher drug retention in the rabbit tear fluid compared to the SM-L lens. In conclusion, the presence of GNPs in contact lenses increased drug uptake from the soaking solution, and improved the in vitro and in vivo release kinetics without affecting the critical properties of the contact lenses for therapeutic application.

摘要

隐形眼镜非常适合用于持续的眼部药物递送，以绕过与滴眼剂治疗相关的问题。然而，通过传统浸泡方法加载的药物（如比马前列素）表现出吸毒率低、突释率高和关键晶状体特性改变。在这项研究中，研究了金纳米粒子 (GNP) 对浸泡溶液中比马前列素的负载/吸收及其从镜片中的释放动力学的影响。在一种方法中，将不同强度的 GNP 溶液加载到比马前列素浸泡溶液中（mM-SS 批次），而在另一种方法中，GNP 在铸造过程中包含在隐形眼镜基质中（mM-GN-L 批次）。GNP 是球形的，平均尺寸为 21.1 nm，zeta 电位为 -20.1 mV。溶胀性、透氧性、与传统浸泡法（SM-L）载药的镜片相比，镜片的透光率和透光率都有所提高。与 SM-L 和 mM-SS 批次相比，mM-GN-L 批次显示从浸泡溶液中吸收药物的显着改善。这体外研究表明，与 SM-L 批次的 24 小时相比，比马前列素释放时间相对较低，持续时间长达 72 小时。随着晶状体中 GNP 量的增加，持续药物释放的能力成比例地提高。GNP 的存在降低了蛋白质的粘附性。在眼部刺激和组织病理学报告（兔模型）中，载有 GNP 的镜片被认为是安全的。此外，与 SM-L 镜片相比，它们在兔泪液中的药物保留率更高。总之，隐形眼镜中 GNP 的存在增加了从浸泡溶液中的药物吸收，并改善了体外和体内的释放动力学，而不会影响隐形眼镜在治疗应用中的关键特性。