Influence of selected drug molecules on human Tear Film Lipid Layer models

Abstract

disertac ̌nı ́ pra ́ce Kamila Riedlova ́ August 2024 Tato dizertac ̌nı ́ pra ́ce zkouma ́ molekula ́rnı ́ interakce ru ̊zny ́ch oftalmologicky ́ch le ́c ̌iv a farmakologicky vy ́znamny ́ch slouc ̌enin s modely lipidove ́ vrstvy slzne ́ho filmu (TFLL) pomocı ́ simulacı ́ molekulove ́ dynamiky (MD). Studie se zame ̌r ̌uje na benzalkonium chlo- ridy (BAKs), latanoprost (LTP), surfaktantovy ́ protein G (SP-G), simulovane ́ v TFLL, a H1 peptid odvozeny ́ od kolicinu U, ktery ́ byl simulova ́n v modelovy ́ch lipidovy ́ch dvoj- vrstva ́ch. MD simulace poskytly podrobne ́ poznatky o interakcı ́ch te ̌chto slouc ̌enin s lipidovy ́mi prostr ̌edı ́mi. Bylo pozorova ́no, z ̌e LTP se integruje do TFLL. LTP vykazoval vy ́znamnou tendenci migrovat a zac ̌len ̌ovat se do lipidove ́ vrstvy a ovlivn ̌ovat tak struk- tura ́lnı ́ dynamiku TFLL. To naznac ̌uje, z ̌e terapeuticka ́ u ́c ̌innost mu ̊z ̌e by ́t zvy 's ̌ena dı ́ky postupne ́mu uvoln ̌ova ́nı ́. Chova ́nı ́ BAKs v TFLL zdu ̊raznilo jejich dvojı ́ roli, ovlivn ̌ujı ́cı ́ jak doda ́vku le ́c ̌iva, tak integritu slzne ́ho filmu (TF). Nas ̌e simulace uka ́zaly, z ̌e molekuly BAKu ̊ pr ̌i ru ̊zny ́ch koncentracı ́ch mohou narus ̌it TFLL, coz ̌ vede ke zme ̌na ́m v lipidove ́m uspor ̌a ́da ́nı ́a potencia ́lnı ́destabilizaci TF. To vyz ̌aduje pec ̌live ́ zva ́z...

of the Dissertation Kamila Riedlova ́ August 2024 This dissertation investigates the molecular interactions of various ophthalmic drugs and pharmacologically significant compounds with models of the tear film lipid layer (TFLL) using molecular dynamics (MD) simulations. The study focuses on benzalko- nium chlorides (BAKs), latanoprost (LTP), surfactant protein G (SP-G), simulated in TFLL, and the H1 peptide derived from colicin U, simulated within model lipid bilay- ers. MD simulations provided detailed insights into the interactions of these compounds with lipid environments. LTP was observed to integrate into the TFLL. LTP demon- strated a significant tendency to migrate and incorporate into the lipid layer, influencing the structural dynamics of TFLL. This suggests that therapeutic efficacy could be en- hanced through sustained release. The behavior of BAKs in TFLL highlighted their dual role, affecting both drug delivery and tear film (TF) integrity. Our simulations showed that BAK molecules at different concentrations could disrupt TFLL, leading to changes in lipid organization and potential TF destabilization. This necessitates careful consideration of the concentration used to balance preservative efficacy with maintaining TF stability. SP-G demonstrated a stabilizing effect on TFLL. By...