Latanoprost incorporates in the tear film lipid layer: An experimental and computational model study

0576891 - ÚFCH JH 2024 RIV NL eng J - Journal Article
Riedlová, Kamila - Saija, Maria Chiara - Olžyńska, Agnieszka - Vazdar, Katarina - Daull, P. - Garrigues, J. - Cwiklik, Lukasz
Latanoprost incorporates in the tear film lipid layer: An experimental and computational model study.
International Journal of Pharmaceutics. Roč. 645, OCT 2023 (2023), č. článku 123367. ISSN 0378-5173. E-ISSN 1873-3476
R&D Projects: GA ČR(CZ) GA21-19854S
Institutional support: RVO:61388955
Keywords : Tear film * Latanoprost * Glaucoma * Tear film lipid layer * Topical delivery * Ophthalmology
OECD category: Physical chemistry
Impact factor: 5.8, year: 2022
Method of publishing: Limited access

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.
Permanent Link: https://hdl.handle.net/11104/0346287