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.

• Klíčová slova
• Glaucoma, Latanoprost, Ophthalmology, Tear film, Tear film lipid layer, Topical delivery,
• MeSH
• antihypertenziva terapeutické užití   MeSH
• glaukom * farmakoterapie   MeSH
• latanoprost terapeutické užití   MeSH
• lidé MeSH
• nitrooční tlak MeSH
• počítačová simulace MeSH
• rohovka MeSH
• slzy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antihypertenziva MeSH
• latanoprost MeSH

Benzalkonium chloride (BAK) compounds are commonly used in topical ophthalmic products as preservatives and stabilizers. BAK mixtures containing several compounds with different alkyl chain lengths are typically used. However, in chronic eye conditions, such as dry eye disease and glaucoma, the accumulation of adverse effects of BAKs was observed. Hence, preservative-free eye drops formulations are preferred. On the other hand, selected long-chain BAKs, particularly cetalkonium chloride, exhibit therapeutic functions, promoting epithelium wound healing and tear film stability. Nevertheless, the mechanism of BAKs influence on the tear film is not fully understood. By employing in vitro experimental and in silico simulation techniques, we elucidate the action of BAKs and demonstrate that long-chain BAKs accumulate in the lipid layer of the tear film model, stabilizing it in a concentration-dependent fashion. In contrast, short-chain BAKs interacting with the lipid layer compromise the tear film model stability. These findings are relevant for topical ophthalmic drug formulation and delivery in the context of selecting proper BAK species and understanding the dose dependency for tear film stability.

• Klíčová slova
• Benzalkonium chloride, Lipid films, Molecular dynamics, Tear film, Tear film lipid layer, Topical ophthalmic formulations,
• MeSH
• benzalkoniové sloučeniny škodlivé účinky   MeSH
• konzervační prostředky farmaceutické * farmakologie   MeSH
• lidé MeSH
• lipidy farmakologie   MeSH
• oční roztoky MeSH
• slzy MeSH
• syndromy suchého oka * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzalkoniové sloučeniny MeSH
• konzervační prostředky farmaceutické * MeSH
• lipidy MeSH
• oční roztoky MeSH

The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops-tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear-air interface.

• Klíčová slova
• Langmuir trough, dilatation rheology, fluorescence microscopy, meibum, molecular dynamics, tear film, tear film lipid layer,
• MeSH
• fluorescenční mikroskopie * metody   MeSH
• kvartérní amoniové sloučeniny chemie   MeSH
• lidé MeSH
• lipidy * chemie   MeSH
• mastné alkoholy chemie   MeSH
• meibomské žlázky metabolismus   MeSH
• poloxamer chemie   MeSH
• simulace molekulární dynamiky * MeSH
• slzy * chemie   MeSH
• teoretické modely MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cetalkonium chloride MeSH Prohlížeč
• kvartérní amoniové sloučeniny MeSH
• lipidy * MeSH
• mastné alkoholy MeSH
• poloxamer MeSH