期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 645, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2023.123367
关键词
Tear film; Latanoprost; Glaucoma; Tear film lipid layer; Topical delivery; Ophthalmology
The tear film lipid layer (TFLL) may serve as a reservoir for latanoprost, facilitating its prolonged release and potentially optimizing glaucoma treatment. These findings have significant implications for the development of new drug delivery systems targeting the TFLL.
Glaucoma is a leading cause of blindness worldwide, with elevated intraocular pressure being a major risk factor for its development and progression. First-line treatment for glaucoma relies on the administration of prostaglandin analogs, with latanoprost being the most widely used. However, before latanoprost reaches the cornea, it must pass through the tear film and tear film lipid layer (TFLL) on the ocular surface. Given the significant lipophilicity of latanoprost, we hypothesize that TFLL could, to a certain extent, act as a reservoir for latanoprost, releasing it on longer time scales, apart from the fraction being directly delivered to the cornea in a postinstillation mechanism. We investigated this possibility by studying latanoprost behavior in acellular in vitro TFLL models. Furthermore, we employed in silico molecular dynamics simulations to rationalize the experimental results and obtain molecular-level insight into the latanoprost-TFLL interactions. Our experiments demonstrated that latanoprost indeed accumulates in the TFLL models, and our simulations explain the basis of the accumulation mechanism. These results support the hypothesis that TFLL can serve as a reservoir for latanoprost, facilitating its prolonged release. This finding could have significant implications for optimizing glaucoma treatment, especially in the development of new drug delivery systems targeting the TFLL.
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