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

• Published in: International journal of pharmaceutics 2023-10, Vol.645, p.123367-123367, Article 123367
• Main Authors: Riedlová, Kamila, Saija, Maria Chiara, Olżyńska, Agnieszka, Vazdar, Katarina, Daull, Philippe, Garrigue, Jean-Sebastien, Cwiklik, Lukasz
• Format: Article
• Language: English
• Subjects: Glaucoma; Latanoprost; Ophthalmology; Tear film; Tear film lipid layer; Topical delivery
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.123367

[Display omitted] •Latanoprost accumulates in the tear film lipid layer models.•Such accumulation could guide optimization of glaucoma treatment.•Combined in vitro and in silico models uncover latanoprost-tear lipids interactions.•The use of oil-in-water nanoemulsions may optimize latanoprost delivery. 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 post-instillation 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.