This study investigates the interaction of two approved and one newly developed latanoprost formulation with in vitro and in silico models of the tear film and tear film lipid layer (TFLL). Latanoprost, a prostaglandin analogue used for intraocular elevated pressure treatment, is topically delivered by nanocarriers within aqueous solutions or emulsions. The study focuses on the impact of these carriers on drug interactions with the tear film and their effect on the TFLL. Three different types of latanoprost carriers, micellar, nanoemulsion, and polymer-based, were compared, and each revealed distinct interaction patterns with the TFLL. Surface pressure kinetics demonstrated a rapid increase for the benzalkonium chloride formulation and a slow rise for the preservative-free variants. Visualization of the acellular in vitro TFLL model revealed different patterns of incorporation for each formulation, indicating unique interaction mechanisms. Molecular dynamics simulations further revealed different mechanisms of drug release in the TFLL between micellar and nanoemulsion formulations. In-depth examination highlighted the role of triglyceride molecules in replenishing the nonpolar layer of the TFLL, which suggests potential improvements in ocular surface compatibility by adjusting the quality and concentration of the oily phase. These findings suggest the potential for optimizing latanoprost formulations by tuning the oily phase-to-surfactant ratio and selecting suitable surfactants.
- MeSH
- antihypertenziva terapeutické užití MeSH
- glaukom * farmakoterapie MeSH
- latanoprost terapeutické užití MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oči * MeSH
- systémy cílené aplikace léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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.
- 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
PURPOSE: To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with healthy controls. METHODS: Observational case-control study. Tear samples were collected by 5 μl microcapillary tube from 24 patients with glaucoma treated by antiglaucoma drops, 9 non-treated patients with ocular hypertension and 45 healthy controls. Tears were analyzed from right eye by multiplex Bio-Plex system for the presence of 6 cytokines: IL1β, IL10, IL4, IFNγ, MIF and VEGF. RESULTS: Significantly higher concentrations of IL1β and IL10 (glaucoma or ocular hypertension vs. healthy controls, p < 0.0001), VEGF (glaucoma vs. ocular hypertension, p < 0.05; ocular hypertension vs. healthy controls, p < 0.02) and MIF (glaucoma vs. healthy controls, p < 0.03) were detected in patients' tears. Both patient groups have activated to a significantly lower extent the Th1 pathway represented by IFNγ than Th2 pathway represented by IL10 (p < 0.001) and, at the same time, the IFNγ/IL4 ratio was significantly increased in healthy controls (p < 0.001) and patients with ocular hypertension (p < 0.02) compared to glaucoma individuals. CONCLUSION: This study shows that secretion of inflammation-related cytokines by conjunctival cells is increased in both, glaucoma and ocular hypertension patients and can be detected in their tears. Nevertheless, data indicates stronger ocular surface inflammation in non-treated follow-up patients diagnosed with ocular hypertension than in glaucoma subjects treated by antiglaucoma drops.
- MeSH
- antihypertenziva terapeutické užití MeSH
- cytokiny metabolismus MeSH
- glaukom s otevřeným úhlem * MeSH
- glaukom * farmakoterapie MeSH
- interleukin-10 metabolismus MeSH
- interleukin-4 metabolismus MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oční hypertenze * MeSH
- oční roztoky MeSH
- slzy metabolismus MeSH
- studie případů a kontrol MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zánět metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- MeSH
- časná diagnóza MeSH
- glaukom * diagnóza farmakoterapie klasifikace prevence a kontrola terapie MeSH
- komorová voda MeSH
- lidé MeSH
- miniinvazivní chirurgické výkony klasifikace metody MeSH
- nitrooční tlak MeSH
- oči patologie MeSH
- testy zrakového pole metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Glaucoma disease therapy frequently involves the application of a glaucoma implant. This approach is effective in terms of reducing the intraocular pressure via the filtering of intraocular fluid from the anterior chamber into the drainage pathways. The basic properties of such implants comprise of long-term stability and the filtering of fluids without the occurrence of undesirable blockages. This study describes the design and production of a novel material for the treatment of glaucoma disease that is based on electrospinning technology. Non-toxic, biocompatible and non-degradable polyvinylidenefluoride (PVDF) was selected as the implant material. The research investigated the resistance of this material to the growth of a fibroblast cell line without the use of antifibrotic agents such as mitomycin C. Three different types of PVDF were electrospun separately and mixed with polyethyleneoxide (PEO), following which the degree of cell growth resistance was evaluated. It was discovered that the fiber layers that contained PVDF blended with PEO evinced a statistically significant difference in metabolic activity compared to the PURE PVDF layers. Only small cell clusters formed on the layers that were resistant to cell fibrotization. As a result of the observed clustering, a new program was developed in MATLAB software for the determination of the number of cells involved in cluster formation, which then allowed for the determination of the spatial dependence between the cells in the form of a point pattern. The study describes a simple technique for the production of composite PVDF+PEO structures suitable for use in the field of glaucoma treatment.
- MeSH
- drenážní implantáty glaukomové * MeSH
- glaukom * farmakoterapie MeSH
- komorová voda MeSH
- lidé MeSH
- mitomycin MeSH
- nitrooční tlak MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Ophthalmic disorders are amid the most common pathologies worldwide. In this regard, hyaluronan (HA) has gained widespread use in eye surgeries and treatment of eye diseases. HA-based materials are well tolerated and show excellent biocompatibility. Therefore, HA is a sought-after component of ophthalmic formulations. However, several parameters have to be adjusted to reach an optimal performance and effectiveness. The complexity of HA properties represents a major challenge for biological and structural characterization. This review covers fundamental aspects and recent developments in HA ophthalmic research. Biological mechanisms underlying the health benefits of HA and their potential therapeutic applications are elaborated. Furthermore, current pharmacokinetic and safety studies are discussed. Noticeably, the benefits of chemical modification and processed HA forms are described to broaden the applications of this unique polysaccharide. The current research challenges and prospects are also outlined and discussed.
- MeSH
- antitumorózní látky chemie metabolismus MeSH
- glaukom farmakoterapie MeSH
- kyselina hyaluronová analogy a deriváty terapeutické užití MeSH
- lidé MeSH
- nosiče léků chemie MeSH
- oční nemoci farmakoterapie MeSH
- oční roztoky chemie MeSH
- viskozita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cíl: Zjistit, zda u hypertenzních glaukomů (HTG) při různých druzích léčby dochází k výraznějšímu poškození některých hodnocených parametrů. Soubor a metodika: Soubor, který tvořilo 36 nemocných (72 očí) HTG, jsme rozdělili do tří skupin: V první skupině byli nemocní léčeni kombinovanou léčbou (latanoprost + timolol, latanoprost + dorzolamid + timolol, dorzolamid + timolol). Skupinu tvořilo sedm žen a pět mužů průměrného věku 64 let (49–81). Ve druhé skupině byli nemocní léčeni betablokátory (carteolol, betaxolol, timolol). Skupinu tvořilo pět žen a pět mužů průměrného věku 62 let (27–77). Ve třetí skupině byli nemocní léčeni prostaglandiny (latanoprost, bimatoprost). Skupinu tvořilo jedenáct žen a tři muži průměrného věku 61 let (61–78). Kritéria pro zařazení do studie byla zraková ostrost 1,0 s případnou korekcí menší než ±3 dioptrie, přibližně stejné změny v zorných polích u všech nemocných, nitrooční tlak (NOT) menší 18 mmHg, žádné jiné oční a neurologické onemocnění. Vrstva nervových vláken (RNFL) na terči zrakového nervu a vessel density (VD) byla změřena pomocí Avanti RTVue XR firmy Optovue. Zjišťovali jsme hodnoty VD v celém obraze (WI) a VD peripapilárně (PP). V obou případech jsme pak měřili všechny cévy (VDa) a malé cévy (VDs). Zorné pole bylo vyšetřeno rychlým prahovým glaukomovým programem přístrojem Medmont M 700. Hodnocen byl overal defect (OD). Statistické zpracování bylo provedeno pomocí multivariantního regresního modelu s adjustací na věk a pohlaví. Jako základ byly vzaty naměřené hodnoty skupiny číslo tři. Výsledky: Statistickým zpracováním jsme zjistili rozdíly v zorných polích jen ve skupině léčených kombinovanou léčbou (p = 0,006) a v RNFL ve skupině léčené betablokátory (p = 0,04).
Aim: The aim of the study was to determine whether hypertensive glaucoma (HTG) with different types of treatment leads to significant damage in any of the evaluated parameters. Sample and methodology: The sample, consisting of 36 HTG patients (72 eyes), was divided into three subgroups: In the first group, patients were treated with combination therapy (latanoprost + timolol, latanoprost + dorzolamide + timolol, dorzolamide + timolol). The group consisted of seven women and five men, with an average age of 64 years (49-81). In the second group, patients were treated with beta-blockers (carteolol, betaxolol, timolol). The group consisted of five women and five men, with an average age of 62 years (27-77). In the third group, patients were treated with prostaglandins (latanoprost, bimatoprost). The group consisted of eleven women and three men, with an average age of 61 years (61-78). Criteria for inclusion in the study were visual acuity of 1.0 with a possible correction of less than ±3 dioptres, approximately the same changes in the visual fields of all patients, an intraocular pressure (IOP) of less than 18 mmHg, and no other ocular or neurological disease. The retinal nerve fibre layer (RNFL) on the optic nerve target and vessel density (VD) was measured using an Avanti RTVue XR from Optovue. We determined the values of VD in whole image (WI) and VD of peripapillary (PP). In both cases, we then measured all vessels (VDa) and small vessels (VDs). The visual field was examined by means of a fast threshold glaucoma program with a Medmont M 700 instrument. In addition to the sum of sensitivities in apostilbs (asb) in the range of 0-22 degrees, the overall visual field defect (OD) was also evaluated. The statistical analysis was carried out using a multivariate regression model with adjustment for age and gender. The measured values of the third group were taken as baseline. Results: In the statistical analysis, we have found differences in visual field in the combination treatment group (p = 0.0006) and differences were recorded for RNFL in the beta-blocker group (p = 0.04).
Zeitschrift für praktische Augenheilkunde & augenärztliche Fortbildung, ISSN 1436-0322 41 Suppl. 2, 2020
3 strany, 1 nečíslovaná strana : ilustrace ; 27 cm
Leták pojednávající o aktualizace poznatků v léčení glaukomu a syndromu suchého oka.
- MeSH
- antiflogistika terapeutické užití MeSH
- glaukom farmakoterapie MeSH
- prostaglandiny terapeutické užití MeSH
- syndromy suchého oka farmakoterapie MeSH
- Publikační typ
- letáky MeSH
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- oftalmologie
- farmacie a farmakologie
- MeSH
- glaukom farmakoterapie MeSH
- lidé MeSH
- makulární degenerace farmakoterapie MeSH
- oční nemoci farmakoterapie MeSH
- prostaglandiny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
- rozhovory MeSH
Nežádoucí účinky lokální antiglaukomové léčby mohou být příčinou špatné spolupráce pacienta v léčebném režimu. To může být důvodem progrese choroby. Pro lepší orientaci lékárníka a praktického lékaře v této oblasti jsou aktuální data z této oblasti sumarizována. Vybrané zvláště významné vztahy a klinické nálezy jsou komentovány.
Subjective symptoms of local side effects of antiglaucomatics may decrease the patients compliance. For better orientation in this issue, the actual data and important clinical findings in this field have been summarized and discussed.
- Klíčová slova
- antiglaukomatika,
- MeSH
- benzalkoniové sloučeniny aplikace a dávkování MeSH
- brimonidin tartarát škodlivé účinky terapeutické užití MeSH
- glaukom * farmakoterapie MeSH
- kombinovaná farmakoterapie škodlivé účinky MeSH
- lidé MeSH
- miotika farmakologie škodlivé účinky terapeutické užití MeSH
- nežádoucí účinky léčiv * MeSH
- prostaglandiny F syntetické klasifikace škodlivé účinky terapeutické užití MeSH
- prostaglandiny škodlivé účinky terapeutické užití MeSH
- sloučeniny síry klasifikace škodlivé účinky terapeutické užití MeSH
- sulfonamidy klasifikace škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH