Comparative Study of Latanoprost Drug Delivery Systems for Glaucoma Treatment and Their Interaction with the Tear Film Lipid Layer Models.

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.

MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension.

PURPOSE   : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. RESULTS: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). CONCLUSIONS: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.

A triple combination of latanoprost, fractional CO2 laser, and platelet-rich plasma in localized vitiligo: A clinical and histopathologic study.

BACKGROUND: Several treatment modalities are available for the treatment of vitiligo due to the lack of a uniformly effective therapy. Topical latanoprost 0.005% is an effective topical treatment. Fractional CO2 laser alone or combined with platelet-rich plasma (PRP) has been proposed as effective adjunctive therapies. OBJECTIVES: We aimed to compare the efficacy of topical latanoprost 0.005% (Ioprost®, Orchidia, Egypt) combined with either add-on fractional CO2 laser or fractional CO2 -PRP versus topical latanoprost monotherapy in the treatment of localized stable vitiligo. PATIENTS/METHODS: The study included 60 patients randomly assigned into three equal groups. Group A patients received topical latanoprost drops only. Group B patients received topical latanoprost drops and fractional CO2 laser sessions at 2-week interval for 3 months. Group C patients received topical latanoprost drops and fractional CO2 laser sessions combined with PRP at a 2-week interval for 3 months. The mean improvement score by the physician was calculated 4 months after the start of the study. Punch skin biopsies were obtained before treatment and 4 months from the beginning of the study and stained with H&E and HMB-45 antibody for evaluation of pigmentation. RESULTS: Significant clinical improvement of vitiligo lesions with significant increase of re-pigmentation were reported in the three treated groups. Latanoprost in combination with fractional CO2 and PRP was associated with more significant therapeutic outcomes than either combined latanoprost and fractional CO2 or latanoprost alone. CONCLUSION: Fractional CO2 laser-PRP enhances the therapeutic efficacy of latanoprost 0.005% in the treatment of localized stable vitiligo.

Narrowband ultraviolet B phototherapy combined with intralesional injection of either latanoprost or platelet-rich plasma for stable nonsegmental vitiligo.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is the cornerstone of vitiligo treatment. Its combination with other treatments usually yields a better response. Latanoprost, a prostaglandin F2α analog, and autologous platelet-rich plasma (PRP) have been reported to be effective for vitiligo. AIM: To evaluate the efficacy of NB-UVB combined with intralesional latanoprost or PRP for stable nonsegmental vitiligo (NSV). METHODS: Sixty patients with stable NSV were recruited and randomly allocated to two equal groups. NB-UVB phototherapy was administered twice a week for all patients. Additionally, group A received intralesional latanoprost injections once weekly, while group B received intralesional autologous PRP injections every 2 weeks. RESULTS: At 24 weeks, excellent repigmentation response was observed in 26.7% and 13.3% of patients in the latanoprost/NB-UVB and PRP/NB-UVB groups, respectively, with no significant difference in degrees of repigmentation between the two groups. However, the Vitiligo Extent Score for a Target Area (VESTA) score was significantly higher in the latanoprost/NB-UVB group (p = .032). Moreover, lesions located on nonacral skin responded significantly better than those on acral skin. Only erythema was significantly higher in the PRP/NB-UVB group, while the recurrence of depigmentation was significantly higher in the latanoprost/NB-UVB group. CONCLUSIONS: Both latanoprost and PRP have the potential to be effective add-on therapies to NB-UVB phototherapy for stable NSV, with latanoprost resulting in a greater repigmentation response and PRP producing a more stable response.

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer). METHODS: This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18-75 years) with open-angle glaucoma or ocular hypertension. RESULTS: Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55-8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61-8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events. CONCLUSIONS: Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life. TRIAL REGISTRATION: The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

Management of androgenic alopecia: a systematic review of the literature.

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

Latanoprost-Loaded Nanotransfersomes Designed for Scalp Administration Enhance Keratinocytes Proliferation.

Latanoprost (LAT) has been shown to have a hypertrichotic effect, which makes it a promising candidate for alopecia treatments. For the first time, LAT has been encapsulated in nanotransfersomes in order to increase its efficacy. Ex vivo skin biodistribution was studied by confocal laser microscopy both in human scalp and pig skin. Results showed that nanotransfersomes increase the penetration of two different fluorochromes, with similar patterns in both species, compared with fluorochrome solutions containing no nanotransfersomes. Nanotransfersomes were stable under accelerated conditions (40 °C/75% RH) and long-term conditions (25 °C/60% RH) for up to 1 year, with no differences in vesicle size and polydispersity when LAT was loaded. Nanotransfersomes increased the LAT cell proliferation effect in HaCaT cell via MAPK signaling pathway. Collectively, our results demonstrate LAT-nanotransfersomes formulation could be a promising therapy for hair growth disorders.

Screening, characterization, and determination of suspected additives bimatoprost and latanoprost in cosmetics using NMR and LC-MS methods.

Recently, many new types of cosmetic illegal additives have been screened in the market. Most of the new additives were new drugs or analogues with very similar structures to other prohibited additives, which were difficult to be identified by liquid chromatography-mass spectrometry (LC-MS) only. Therefore, a new strategy is proposed, which is chromatographic separation combined with nuclear magnetic resonance spectroscopy (NMR) structural identification. The suspected samples were screened by ultra-high-performance liquid chromatography tandem high-resolution mass spectrometry (UPLC-Q-TOF-MS), followed by purification and extraction through silica-gel column chromatography and preparative high-performance liquid chromatography (HPLC). Finally, the extracts were identified unambiguously by NMR as bimatoprost and latanoprost, which were identified to be new cosmetic illegal additives in eyelash serums in China. Meanwhile, bimatoprost and latanoprost were quantified by high-performance liquid chromatography tandem triple quadrupole mass spectrum (HPLC-QQQ-MS/MS). The quantitative method demonstrated good linearity in the range of approximately 0.25-50 ng/mL (R2 > 0.9992), with limit of detection (LOD) and limit of quantification (LOQ) values of 0.01 and 0.03 mg/kg, respectively. The accuracy, precision, and reproducibility were confirmed to be acceptable.

The effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% at a tertiary glaucoma center.

PURPOSE: To assess real-world effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% (FCNL) in management of glaucoma patients in a tertiary eye care center. METHODS: This retrospective cohort study included glaucoma patients initiated on FCNL from January 2018 to July 2021 with at least 1-month follow-up. Demographic and clinical data were collected at baseline and at follow-up visits through 12 months. Patient-solicited side effects were recorded at each visit. Maximum glaucoma pharmacotherapy was defined as surgery/laser being the next treatment option following an intensive pharmacotherapy regimen, or when pharmacotherapy could not be increased due to allergy/intolerance or all pharmacologic mechanisms already being in use. RESULTS: Seventy-nine eyes of 47 patients were included. Mean age was 67.7 ± 14.7 years. Baseline IOP was 18.7 ± 4.9 mmHg; mean change in IOP (∆IOP) each study visit compared to baseline ranged from - 1.6 ± 3.5 to - 4.4 ± 4.1 mmHg (all p < 0.05). The eyes on maximum glaucoma pharmacotherapy (73.4%) had similar ∆IOP compared to those on non-maximal therapy at each visit (p > 0.2 for all). Forty-three (54.4%) eyes were switched from a prostaglandin analog alone, producing a 1-month IOP reduction of - 4.7 ± 3.9 mmHg at 1 month which remained significant at each visit for the 12-month study period (all p < 0.05). Across all study visits, conjunctival hyperemia was documented in 26 (32.9%) eyes. Subjective blurry vision was reported in 22 (27.8%) eyes without significant worsening of visual acuity at any visit (all p > 0.05). Six (7.6%) and 7 (8.9%) eyes required further medical or surgical/laser intervention, respectively. Kaplan-Meier analysis revealed no significant difference in the need for subsequent medical or surgical intervention between those on maximum and non-maximal pharmacotherapy (p > 0.4). CONCLUSION: FCNL was well-tolerated and demonstrated a significant and sustained reduction in IOP, even as last-line therapy before incisional or laser surgery in those on maximum glaucoma pharmacotherapy. FCNL is a viable treatment option for glaucomatous eyes before consideration of surgical intervention.

A Non-Inferiority Study of Combination of Latanoprost and Timolol Formulation to Their Separate Use in Drug-Naive Primary Open Angle Glaucoma and Ocular Hypertension Nigerian Patients. {RCT 93803536 (Nigeria Clinical Trial Registry)}.

BACKGROUND: Control of intraocular pressure continues to be the mainstay of the management of primary open-angle glaucoma. It is also one of the key factors to consider in the diagnosis and risk of conversion of ocular hypertension to glaucoma (POAG). Medical management of IOP control is central to the treatment of POAG especially in resource-poor countries. AIM: This study aimed to demonstrate the non-inferiority of a fixed combination of front-line drugs in the medical management of glaucoma (latanoprost and timolol) compared to concomitant use of the same drugs. METHODOLOGY: It was a double-blind, randomized clinical trial (RCT) in which 116 sequentially consenting participants 40 years and above were recruited and randomized to receive either a fixed combination (group A) or a concomitant combination of latanoprost and timolol (group B). The study was carried out across two tertiary centers in southwest Nigeria. RESULTS: One hundred and fifteen (115) patients were analysed, 58 in group A and 57 in group B. The mean age of participants was 57.9 (± 11.5) years. There were 51 (44.3%) females. Primary open-angle glaucoma (POAG) was the diagnosis in 88 (76.5%) of the participants. No statistically significant difference between the two groups at recruitment. Mean IOP reduction from baseline to day 28 was -17.30 ± 7.8 (95% CI: -15.37 to -19.15), and -14.59 ± 6.1 (95% CI: -12.98 to -16.19) for groups A and B. Group A thus had a 54.97% IOP reduction from baseline values while group B had 51.81% (p = 0.770). The mean intergroup difference (MeD) in IOP reduction (µA - µB) between the two groups on day 28 was 2.05 ± 5.74 (95% CI: 0.6 - 1.61) p=0.04. CONCLUSION: The study was able to demonstrate a noninferiority relationship between the fixed combination dosage form of latanoprost and timolol as compared to the concomitant dosage forms.

CONTEXTE: Le contrôle de la pression intraoculaire reste le pilier de la prise en charge du glaucome à angle ouvert primaire. C'est également l'un des principaux facteurs à considérer dans le diagnostic et le risque de conversion de l'hypertension oculaire en glaucome (POAG). La gestion médicale du contrôle de la pression intraoculaire est essentielle dans le traitement du POAG, surtout dans les pays à ressources limitées. OBJECTIF: Cette étude visait à démontrer la non-infériorité d'une combinaison fixe de médicaments de première ligne dans la gestion médicale du glaucome (latanoprost et timolol) par rapport à l'utilisation concomitante des mêmes médicaments. MÉTHODOLOGIE: Il s'agissait d'un essai clinique randomisé en double aveugle dans lequel 116 participants consécutifs âgés de 40 ans et plus ont été recrutés et répartis de manière aléatoire pour recevoir soit une combinaison fixe (groupe A) soit une combinaison concomitante de latanoprost et de timolol (groupe B). L'étude a été menée dans deux centres tertiaires du sud-ouest du Nigeria. RÉSULTATS: Cent quinze (115) patients ont été analysés, 58 dans le groupe A et 57 dans le groupe B. L'âge moyen des participants était de 57,9 (± 11,5) ans. Il y avait 51 (44,3%) femmes. Le glaucome à angle ouvert primaire (POAG) a été diagnostiqué chez 88 (76,5%) des participants. Aucune différence statistiquement significative entre les deux groupes au moment du recrutement. La réduction moyenne de la pression intraoculaire entre le début et le jour 28 était de -17,30 ± 7,8 (IC à 95% : -15,37 à ­19,15) et de -14,59 ± 6,1 (IC à 95% : -12,98 à -16,19) pour les groupes A et B. Le groupe A a ainsi présenté une réduction de 54,97 % de la PIO par rapport aux valeurs initiales tandis que le groupe B a enregistré 51,81 % (p = 0,770). La différence moyenne intergroupes (DMI) dans la réduction de la PIO (µA ­ µB) entre les deux groupes au jour 28 était de 2,05 ± 5,74 (IC à 95% : 0,6 ­ 1,61) p = 0,04. CONCLUSION: L'étude a pu démontrer une relation de noninfériorité entre la forme posologique fixe de latanoprost et de timolol par rapport aux formes posologiques concomitantes. MOTS-CLÉS: Glaucoma, Hypertension oculaire, Contrôle de la PIO, Nigérians, Latanoprost, Timolol, Hypotenseurs oculaires, Combinaison fixe, Patients naïfs aux médicaments.

[The value of lamina cribrosa in the diagnosis and treatment of glaucoma. Remodeling of lamina cribrosa collagen and approaches to its therapeutic treatment]. / Znachenie struktury reshetchatoi membrany sklery v diagnostike i lechenii glaukomy. Remodelirovanie kollagena reshetchatoi membrany i puti terapevticheskogo vozdeistviya na nego.

Among the first structures suffering damage with an increase in intraocular pressure (IOP) and in early stage of glaucoma are the lamina cribrosa (LC) and peripapillary sclera (ppScl). Changes in these structures occur at the molecular and cellular level. Extracellular matrix (ECM) is the basis of connective tissue, provides mechanical support for the cells, facilitates intercellular interactions and transport of chemicals, including in LC and ppScl. Mechanical stress causes remodeling and disorganization of the ECM, which leads to changes in the structure of the tissue itself, an increase in its rigidity and a decrease in elasticity. Taking into account the molecular and cellular mechanisms of damage to LC and ppScl, various researchers have developed strategies and tactics for therapeutic intervention on these structures, contributing to a decrease in ECM secretion and, as a consequence, suspension of their remodeling. These approaches may in the future form the basis for the treatment of glaucomatous optic neuropathy.

[Comparison of the effectiveness and safety of glaucoma drugs in the therapy of primary open-angle glaucoma]. / Sravnenie effektivnosti i bezopasnosti primeneniya protivoglaukomnykh preparatov v terapii pervichnoi otkrytougol'noi glaukomy.

The rise in the number of glaucoma drugs complicates the choice that the ophthalmologists have to do. PURPOSE: The study compares the effectiveness, safety and usability of the Russian latanoprost drug Trilaktan and the drug Xalatan in monotherapy for patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH). MATERIAL AND METHODS: This is a multicenter observational study of the effectiveness and safety of eye drops Trilaktan (Groteks, Russia) and Xalatan (Pfizer MFG. Belgium N.V., Belgium) in monotherapy for patients with POAG of early and moderate stages or OH. The maximum duration of the regimen for the studied drugs was 87 days. The study included 76 patients: 56 (74%) women and 20 (26%) men aged 50-84 years (mean age 66.3±1.3 years). The groups were homogeneous in demographic, anthropometric and vital indicators. Effectiveness was assessed by the trends in intraocular pressure (IOP) changes, safety - by analyzing the adverse events, usability and ease of use - by the questionnaires the study patients filled. RESULTS: Both drugs investigated in this study decrease IOP by a mean of 6-8 mm Hg depending on tonometry method, with difference not exceeding 0.55 mm Hg. The proportion of patients with IOP decreased by 30% and more from the baseline level was 89.5% in both groups. The differences between the indicators of drug usability (by McMonnies conjunctival hyperemia scale, tear break-up time (TBUT), punctate keratopathy, OSDI questionnaire results) were insignificant, and the observed changes did not decrease the tolerability of the studied drugs. The patients using Trilaktan also commended the usability of the included eye drops dispenser. CONCLUSIONS: The results of this study allow a conclusion that the effectiveness and safety of Trilaktan (Groteks, Russia) eye drops are equal to those of Xalatan (Pfizer MFG. Belgium N.V., Belgium) eye drops in patients with POAG of early and moderate stages or OH. Trilaktan is easy to use thanks to the included eye drops dispenser.

Effect of topical latanoprost on choroidal thickness and vessel area in Guinea pigs.

The aim of this study was to investigate the effect of latanoprost, an ocular hypotensive agent and prostaglandin analog, on choroidal thickness and structure in young adult guinea pigs. Young (three-month-old) guinea pigs (n = 10) underwent daily monocular treatment with topical 0.005% latanoprost for 2 weeks, followed by a washout period of 2 weeks. Tonometry (iCare) and retinoscopy were undertaken to monitor intraocular pressure (IOP) and refractive error (recorded as spherical equivalent refractive error; SER), respectively. Axial length (AL) and choroidal thickness (ChT) were measured using high frequency A-scan ultrasonography, with additional ChT data, as well as choroidal vessel (ChV) areas obtained from posterior segment imaging using Spectral Domain-Optical Coherence Tomography (SD-OCT). Image J was used to analyze SD-OCT images. As expected, latanoprost significantly reduced IOP in treated eyes. Mean interocular IOP difference (±SE) changed from -0.40 ± 0.31 mmHg at baseline to -2.23 ± 0.43 mmHg after 2 weeks of treatment (p = 0.05). However, SER and AL were unaffected; interocular difference changed from 0.41 ± 0.58 to 0.38 ± 0.43 D and from -0.002 ± 0.02 mm to -0.007 ± 0.01 mm (p > 0.05), respectively. Latanoprost had minimal effect on ChT. Interocular ChT differences were 0.01 ± 0.06 µm at baseline and 0.04 ± 0.06 µm after 2 weeks of treatment (SD-OCT; p > 0.05). However, treated eyes had significant increased ChV areas; interocular differences changed from -0.76 ± 69.2 to 100.78 ± 66.9 µm2 after treatment (p = 0.04). While this study was limited to otherwise untreated young adult guinea pigs, the possibility that choroidal vessel enlargement contributes to the previously reported inhibitory effect of topical latanoprost on myopia progression in young guinea pigs warrants investigation.

Effects of PPAR-γ and RXR-α on mouse meibomian gland epithelial cells during inflammation induced by latanoprost.

The purpose of this study is to investigate the effects of latanoprost on the secretion of cytokines and chemokines from meibomian gland epithelial cells, and to evaluate the modulation of peroxisome proliferator-activated receptor γ (PPAR-γ) and retinoid X receptor α (RXR-α) during latanoprost-induced inflammation. Mouse meibomian gland epithelial cells were cultured in proliferation and differentiation medium, respectively. Cells were exposed to latanoprost, rosiglitazone (PPAR-γ agonist), or LG100268 (RXR-α agonist), respectively. The expression of IL-6, IL-1ß, TNF-α, MMP-9, MCP-1, and CCL-5 were detected by real-time PCR and ELISA. The effect of latanoprost, rosiglitazone, LG100268, and inflammatory cytokines on the differentiation of meibocyte were evaluated by related gene expression and lipid staining. The expression of Keratin-1, 6, 17 protein was detected by western immunoblotting. The results showed that the above cytokines could be induced by latanoprost in meibomian gland epithelial cells. LG100268 and rosiglitazone could inhibit the production of IL-6 and TNF-α induced by latanoprost, respectively. Latanoprost suppressed the expression of differentiation-related mRNA through a positive feedback loop by enhancement of COX-2 expression via FP receptor-activated ERK signaling. The expression of Keratin-17 was upregulated by rosiglitazone and suppressed by LG100268. The application of IL-6 and TNF-α showed negative effects on lipid accumulation in meibomian gland epithelial cells. These results demonstrated that latanoprost could induce inflammation and suppress differentiation of mouse meibomian gland epithelial cells. The activation of PPAR-γ and RXR-α showed an anti-inflammatory effect, showing a potential role to antagonize the effect of latanoprost eyedrops on meibomian gland epithelial cells.

The effect of latanoprost 0.005% solution in the management of scalp alopecia areata, a randomized double-blind placebo-controlled trial.

Alopecia areata (AA) is a recurrent chronic disease that affects hair follicles and results in hair loss. Make an increase in the number, thickness, and length of eyelashes is an important side effect of latanoprost eye drop. This study aimed to evaluate the effect of hypertrichosis property of latanoprost in the treatment of scalp AA. In this randomized double-blind placebo-controlled trial, 30 participants with scalp AA assigned to receive either topical latanoprost 0.005% solution or placebo for 12 weeks. In both arms, patients also received clobetasol 0.05% cream in isopropyl alcohol (1:1). The hair loss area pictured at baseline and the end of the fourth, eighth, and twelfth weeks. According to the images, the dermatologist assessed the hair loss area, hair density, and the severity of alopecia. Latanoprost significantly increased hair density (37.2 ± 26.1 vs. 14.6 ± 18.6) and regrowth (58.3 ± 39.3 vs. 21.6 ± 24.1) based on the Severity of Alopecia Tool (SALT) system compared to the control group (p = 0.03 and 0.02, respectively). However, there were no significant differences between the two groups in reduction in the hair loss area and SALT, and the incidence of side effects (p = 0.718, 0.262, and ≥0.99, respectively). Results showed the acceptable safety and efficacy of latanoprost 0.005% solution to increase hair density and regrowth. So, it could be safely used for the management of scalp AA.

Comparison of efficacy, safety and satisfaction of latanoprost versus minoxidil, betamethasone and in combination in patients with alopecia areata: A blinded multiple group randomized controlled trial.

Alopecia areata (AA), a polygenic and chronic autoimmune disease and there is no definitive cure. We aimed to evaluate latanoprost effects in patients with AA. In this controlled randomized double-blind clinical trial, we enrolled patients with AA randomly assigned to six groups of 18; Group 1 received latanoprost eye drops; group 2 minoxidil 5% solution; group 3 latanoprost eye drops and minoxidil 5% solution; group 4 betamethasone and minoxidil 5% solution; group 5 betamethasone solution and latanoprost eye drops; group 6 (the control group) betamethasone solution. The alopecia severity in patients before and after treatment was assessed by severity of alopecia tool (SALT). One hundred and eight patients, 50% male (mean age: 32.6 ± 10.4) were studied. The overall SALT score decreased in all. After 2 weeks, patients receiving betamethason-minoxidil and betamethason-latanoprost showed more decline in their SALT than other groups. In final, there was statistically significant difference among betamethasone-latanoprost group with minoxidil, betamethasone-minoxidil and betamethasone groups. Regrowth was higher in latanoprost and betamethasone-latanoprost groups than minoxidil. Topical latanoprost added to therapeutic efficacy of topical betamethason and minoxidil in treating patchy AA, suggesting it being beneficial and safe adjuvant therapy and add to efficacy of topical treatments without any adverse effects.

A novel ophthalmic latanoprost 0.005% nanoemulsion: a cytotoxicity study.

BACKGROUND: Benzalkonium chloride (BAK), the most commonly used preservative in anti-glaucoma eye drops, inflicts damage to the ocular surface. A novel anti-glaucoma formulation that avoids the use of BAK has been developed. The aim of this study was to evaluate the cytotoxicity of this formulation and to compare it with an ophthalmic solution containing BAK. METHODS: Two different latanoprost eye drops were used: one ophthalmic solution (LSc) containing BAK 0.02% and one ophthalmic nanoemulsion (LNe) with a soft preservative (potassium sorbate 0.18%). Human epithelial conjunctival cells were incubated for 15, 30, and 60 min with either LSc or LNe. The cytotoxicity was determined by MTT assay. Cell death was measured by flow cytometry using annexin V-FITC and propidium iodide. RESULTS: The values of cell viability and proliferation obtained from cells exposed to LNe were between 80 and 90% relative to the control group, whereas values obtained from cells exposed to LSc were around 30% at all study times (p < 0.05 at 15 and 30 min; p < 0.01 at 60 min). The percentage of viable cells decreased significantly when cells were incubated with LSc compared with cells incubated with LNe at all the study times, while the percentage of cells in late apoptosis/necrosis increased significantly in cells exposed to LSc compared to LNe. CONCLUSIONS: The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.

Comparative effects of latanoprost and latanoprostene bunod on intraocular pressure and pupil size in ophthalmologically normal Beagle dogs.

OBJECTIVE: To compare effects of latanoprost, a topical prostaglandin analogue (PGA) commonly used to treat glaucoma and lens instability in dogs, and latanoprostene bunod, a novel PGA with a nitric oxide-donating moiety, on intraocular pressure (IOP) and pupil diameter (PD). ANIMALS STUDIED: Ten ophthalmologically normal Beagle dogs. PROCEDURES: Dogs were treated twice a day for 5 days in a randomly selected eye with either latanoprost or latanoprostene bunod. After a 6-week washout period, dogs were treated with the opposite drug. IOP and PD were measured at treatment times, at midday on days 1 and 5, and for 6 days post-treatment. RESULTS: Both drugs significantly decreased IOP and PD. At midday on day 5 of treatment, mean IOP in eyes treated with latanoprost was 4.5 mmHg lower than the fellow eye and 3.0 mmHg lower than the same eye at baseline, while mean IOP in eyes treated with latanoprostene bunod was 5.5 mmHg lower than the fellow eye and 3.6 mmHg lower than baseline. Mean PD was 0.94 mm in eyes treated with latanoprost and 0.76 mmHg in eyes treated with latanoprostene bunod. There was no significant difference between the two drugs for either parameter at that time point (p = .372 and .619, respectively, for IOP relative to control and to baseline; p = .076 for PD) or when analyzed longitudinally. Significant diurnal variation in PD was noted and may have implications for treatment of lens' instability. CONCLUSIONS: Latanoprost and latanoprostene bunod produce similar IOP reduction and miosis in normal canine eyes.

Sustained latanoprost release from PEGylated solid lipid nanoparticle-laden soft contact lens to treat glaucoma.

Contact lens have been proposed as a mean of ocular drug delivery, but the conventional soaking method to load hydrophobic drugs, such as latanoprost shows low drug loading and high burst release with alteration in the critical lens properties. In this paper, a novel latanoprost-loaded PEGylated solid lipid nanoparticles (LP-pSLNs) were developed to increase the latanoprost loading capacity of contact lenses (LP-pSLN-L), while also sustaining ocular drug delivery. The pSLNs were spherical in shape with an average size of 105‒132 nm (nanometer) and a zeta potential ranging from ‒29.1 to ‒26.7 mV (millivolt). The LP-pSLNs led to improved swelling, transmittance, and protein adherence of the lens compared to the non-pegylated SLNs congeners (LP-SLN-L) and conventional soaked lens (LP-SM-L). The LP-SM-L lens showed low drug loading, high burst release, and a short release duration of 24 h. The LP-SLN-L and LP-pSLN-L lenses showed high drug uptake and sustained drug release up to 120 h and 96 h, respectively. The pegylation reduced the size of nanoparticles and improved the drug loading capacity, while the release rate was high in the initial hours. The LP-pSLN-L lens was found to be safe based in histopathological studies. In animal studies, the LP-pSLN-10-L batch showed high drug concentration at all-time points up to 96 h compared to the LP-SM-L and eye drop solution. In conclusion, pSLNs improved the latanoprost loading in the contact lens and showed sustained drug release, and thus can be used as a substitute to eye drop therapy.

[Neuroprotective properties of latanoprost]. / Neiroprotektornye svoistva latanoprosta.

Glaucoma is the main cause of irreversible blindness in the world. Latanoprost - an ester prodrug of prostaglandin F2α (PGF2α) - was the first prostaglandin analogue used to treat glaucoma. The review shows that latanoprost possesses direct neuroprotective properties such as blocking the entry of calcium ions into neurons and inhibiting the action of caspase-3, inhibiting the activity of cyclooxygenase and activation of polypeptide 2B1 (OATP2B1) and Klotho protein. It is emphasized that when the drug is instilled into the eye, the concentration of the drug inside the vitreous body is twice as high as what is required to ensure the survival of retinal ganglion cells.