scholarly journals Ocular Application of Oleuropein in Dry Eye Treatment: Formulation Studies and Biological Evaluation

2021 ◽  
Vol 14 (11) ◽  
pp. 1151
Author(s):  
Susi Burgalassi ◽  
Erica Zucchetti ◽  
Elena Birindelli ◽  
Silvia Tampucci ◽  
Patrizia Chetoni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aqueous Solution ◽  
Dry Eye ◽  
Biological Evaluation ◽  
Point Of View ◽  
Eye Drops ◽  
Scanning Calorimetry ◽  
Lipid Film ◽  
Solution Methods ◽  
Ph Buffer

Background. Oleuropein is already known for its numerous pharmacological properties, but its activity in the ocular field has not yet been investigated. The study aims to verify a possible use of oleuropein (OLE)-based eye drops both in terms of efficacy in dry eye syndrome and stability in aqueous solution. Methods. OLE was co-precipitated with HP-β-cyclodextrin, and the obtained complex was encapsulated into liposomes prepared by hydration of a lipid film composed of Lipoid S100 and cholesterol with different pH buffer solutions. The hydrated vesicles were shrunk by ultrasonication or extrusion. The preparations were characterized from the physicochemical point of view by subjecting them to differential scanning calorimetry, ATR-FTIR, dynamic light scattering analysis, and microscopy. Subsequently, OLE protective activity against hyperosmotic and oxidative stress on rabbit corneal epithelial cells (RCE) was evaluated. Results. The liposomal vesicles obtained after extrusion showed a tendency towards greater encapsulation efficiency (up to 80.77%) compared to that obtained by sonication, and the liposomes hydrated in pH 5.5 solution tended to incapsulate more than the neutral ones. Ultrasonication produced two-dimensional populations of liposomes, the largest of which reached 2149 nm. On the contrary, the extruded liposomes showed homogeneous diameters of about 250 nm. Complexation with cyclodextrin and subsequent encapsulation in liposomes greatly increased the OLE stability in aqueous solution, especially at 4 °C and for the extruded formulations. OLE aqueous solution (OLE7.4-sol, reference) and neutral extruded liposomes (F7.4-e) were well tolerated on RCE cells. Moreover, OLE was able to control the effects of hyperosmolarity on ocular surface cells and to prevent oxidative stress-induced loss of cell viability.

scholarly journals Efficacy of a Novel Integrated Active Herbal Formulation in Experimentally Induced Rat Model for Dry Eye Disease

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 441-441
Author(s):  
Abhijeet Morde ◽  
Omer Ersin Muz ◽  
Cemal Orhan ◽  
Fusun Erten ◽  
Mehmet Tuzcu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dry Eye ◽  
Rat Model ◽  
Tear Film ◽  
Oral Dosage ◽  
Eye Drops ◽  
Dependent Manner ◽  
Dry Eyes ◽  
Health Technologies ◽  
Active Formulation

Abstract Objectives Dry eye is common condition of eye with insufficient production of tears leading to inadequate lubrication of eyes. It is chronic in nature & may be associated with discomfort & eye redness, blurred vision & tear film instability leading to potentially damaged ocular surfaces. Inflammation & oxidative stress play significant role in pathogenesis of disease by causing ocular surface disruption. Traditional Rx for dry eyes such as artificial tears, punctual plugs, prescription eye drops, etc. doesn't adequately address underlying causes of dry eyes. Further many of treatments are in form of eye drops that require regular administration to eyes, which is inconvenient & contains preservatives that further irritate eyes. We evaluated integrated active formulation administered orally to alleviate symptoms of dry eyes in rat model. Methods We used proprietary formulation technology to blend multiple ingredients into an integrated oil suspension (OS) that can be conveniently used in an oral dosage form. Ingredients included bioavailable form of Curcumin, Lutein/Zeaxanthin (L/Z) and Vit D3 formulated as an integrated product. Dry eye condition was created by administration of BAK (benzalkonium chloride) to eyes of female Wistar rat twice daily for 14 days, followed by initiation of supplementation by administering integrated dry eye formulation by oral gavage for 4 weeks at dose of 100 & 200 mg/kg b.w. to evaluate effect of this novel formulation. 7 rats were included in each group. Results There was significant improvement in tear volume, tear breakup time, tear film integrity & reduced overall inflammation, histopathological examination with supplementation. Our formulation helped in lowering oxidative stress as evidenced by significant reduced serum & corneal MDA, increased corneal SOD & corneal GPx. Levels of inflammatory cytokines such as NF-κB, TNF-α, IL-1β, IL-6 & IL-8 were significantly reduced & protective proteins such as MUC1, MUC4, MUC5AC and MMP-9 were restored by supplementation with integrated dry eye formulation which were otherwise lowered in dry eye condition. Conclusions Our results strongly suggest that our novel integrated active formulation of Curcumin, L/Z, Vit D3 is effective in alleviating symptoms of dry eye condition with multi-modal mechanism of action in dose dependent manner. Funding Sources OmniActive Health Technologies Limited.

scholarly journals Improving Stability of Tear Film Lipid Layer via Concerted Action of Two Drug Molecules: A Biophysical View

2020 ◽  
Vol 21 (24) ◽  
pp. 9490
Author(s):  
Petar Eftimov ◽  
Agnieszka Olżyńska ◽  
Adéla Melcrová ◽  
Georgi As. Georgiev ◽  
Philippe Daull ◽  
...  
Keyword(s):  
Dry Eye ◽  
Tear Film ◽  
Eye Drops ◽  
Active Components ◽  
Lipid Film ◽  
Drug Molecules ◽  
Air Interface ◽  
Oil In Water ◽  
Surface Active ◽  
Dynamics Simulations

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.

scholarly journals The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares

2021 ◽  
Vol 13 ◽  
pp. 251584142110127
Author(s):  
Preeya K. Gupta ◽  
Nandini Venkateswaran
Keyword(s):  
Drug Delivery ◽  
Dry Eye ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Eye Drops ◽  
Short Term ◽  
Short Term Treatment ◽  
Loteprednol Etabonate ◽  
Mucus Barrier

The tear film, which includes mucins that adhere to foreign particles, rapidly clears allergens and pathogens from the ocular surface, protecting the underlying tissues. However, the tear film’s ability to efficiently remove foreign particles during blinking can also pose challenges for topical drug delivery, as traditional eye drops (solutions and suspensions) are cleared from the ocular surface before the drug can penetrate into the conjunctival and corneal epithelium. In the past 15 years, there has been an increase in the development of nanoparticles with specialized coatings that have reduced affinity to mucins and are small enough in size to pass through the mucus barrier. These mucus-penetrating particles (MPPs) have been shown to efficiently penetrate the mucus barrier and reach the ocular surface tissues. Dry eye disease (DED) is a common inflammatory ocular surface disorder that often presents with periodic flares (exacerbations). However, currently approved immunomodulatory treatments for DED are intended for long-term use. Thus, there is a need for effective short-term treatments that can address intermittent flares of DED. Loteprednol etabonate, an ocular corticosteroid, was engineered to break down rapidly after administration to the ocular surface tissues and thereby reduce risks associated with other topical steroids. KPI-121 is an ophthalmic suspension that uses the MPP technology to deliver loteprednol etabonate more efficiently to the ocular tissues, achieving in animal models a 3.6-fold greater penetration of loteprednol etabonate to the cornea than traditional loteprednol etabonate ophthalmic suspensions. In clinical trials, short-term treatment with KPI-121 0.25% significantly reduced signs and symptoms of DED compared with its vehicle (placebo). Recently approved KPI-121 0.25%, with its novel drug delivery design and ease of use, has the potential to effectively treat periodic flares of DED experienced by many patients.

scholarly journals Comprehensive Evaluation of Biological Effects of Pentathiepins on Various Human Cancer Cell Lines and Insights into Their Mode of Action

2021 ◽  
Vol 22 (14) ◽  
pp. 7631
Author(s):  
Lisa Wolff ◽  
Siva Sankar Murthy Bandaru ◽  
Elias Eger ◽  
Hoai-Nhi Lam ◽  
Martin Napierkowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Biological Effects ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Human Cancer Cell ◽  
Strand Breaks ◽  
Human Cancer Cell Lines

Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.

scholarly journals Dry eye disease among Glaucoma patients on topical hypotensive medications, in a tertiary hospital, Ethiopia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Miraf Sahlu ◽  
Abeba T. Giorgis
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Signs And Symptoms ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Eye Drops ◽  
Schirmer Test ◽  
Ocular Surface Disease Index ◽  
Cross Sectional ◽  
Corneal Staining

Abstract Background Dry eye disease is a multifactorial disease; causing various ocular symptoms with potential damage to the ocular surface. Applying hypotensive eye drops are presumed to initiate or exacerbate existing dry eye disease. The purpose of this study was to determine the frequency of signs and symptoms and severity of dry eye disease among glaucoma patients on topical hypotensive medications and controls. Methods A cross-sectional comparative study, involving 320 glaucoma patients and controls. Ocular Surface Disease Index (OSDI) symptoms score and Schirmer, tear breakup time and corneal staining tests were used to assess dry eye disease. Data was analyzed using SPSS version 24 software; p-value less than 0.05 was considered as statistically significant. Results Among the 160 study glaucoma patients, the mean duration of topical hypotensive medication use was 5.2 ± 5.21 years (range, 4 months - 32 years). Mild to severe level of OSDI score was found in 122 (76%) glaucoma patients and in 137 (86%) controls (p = 0.033). Mild to sever abnormal clinical tests in the glaucoma patients and control, respectively, were 106 (66%) vs 80 (50%) corneal staining (p = 0.045), 79 (49%) vs 72 (45%) TBUT (p = 0.021), and 91 (57%) vs 83 (52%) Schirmer test (p = 0.242). Test results at the level of sever: 2 (1%) vs 0 (0%) corneal staining, 50 (31%) vs 39 (24%) TBUT and 65 (41%) vs 60 (38%) Schirmer test in the glaucoma patents and controls, respectively. Corneal staining and TBUT had correlation with the number of drugs (p = 0.004 and 0.031, respectively), and more relationship of the two tests with total number of drops applied per day (p = 0.01 and p <  0.001, respectively). Patients on pilocarpine and timolol had more corneal staining and lower TBUT [(p = 0.011 and p <  0.001) and (p = 0.04 and 0.012), respectively]. Conclusions The study has identified glaucoma patients to be more affected by dry eye disease than non-glaucoma patients, and presence of significantly lower TBUT and higher corneal staining in the glaucoma patients on multidrops and multidose per day. We recommend consideration of evaluation and management of DED for glaucoma patients on multidrops and multidose hypotensive medications.

scholarly journals A Meta-Analysis of the Efficacy of Hyaluronic Acid Eye Drops for the Treatment of Dry Eye Syndrome

2021 ◽  
Vol 18 (5) ◽  
pp. 2383
Author(s):  
Yun-Jung Yang ◽  
Won-Young Lee ◽  
Young-jin Kim ◽  
Yeon-pyo Hong
Keyword(s):  
Hyaluronic Acid ◽  
Confidence Interval ◽  
Dry Eye ◽  
Test Scores ◽  
Meta Analysis ◽  
Mean Difference ◽  
Dry Eye Syndrome ◽  
Eye Drops ◽  
Cochrane Central Register ◽  
Standard Mean Difference

Hyaluronic acid (HA) is commonly used for treating dry eye syndrome (DES). This meta-analysis was performed to compare the efficacies of HA- and non-HA-based eye drops, including saline and conventional artificial tears (ATs), for the treatment of dry eye disease. Eight databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials, DBpia, KoreaMed, KMBASE, RISS, KISS) were searched for studies comparing the efficacies of HA- and non-HA-based ATs in patients with DES published up to September 2020. Two independent reviewers assessed the quality and extracted the relevant data. The mean differences of Schirmer’s (SH) test scores, tear breakup times (TBUT), corneal fluorescein staining scores (Oxford scale, 0–4), and ocular surface disease indexes were calculated. The standard mean difference and 95% confidence interval were calculated using a random effect model. Nineteen studies, including 2078 cases, were included. HA eye drops significantly improved tear production compared with non-HA-based eye drops (standard mean difference (SMD) 0.18; 95% confidence interval (CI) 0.03, 0.33). In a subgroup analysis, the SH test scores and TBUT values after using HA significantly increased compared to those measured after using saline (SMD 0.27; 95% CI 0.05, 0.49 and SMD 0.28; 95% CI 0.03, 0.52, respectively). Based on these results, HA eye drops may be superior to non-HA eye drops including normal saline and ATs. Further research is needed to assess the efficacies stratified by age, treatment duration, the severity of dry eye, and optimal dosages.

scholarly journals Comparison of treatment efficacy between 100% platelet-rich plasma and 100% serum eye drops in moderate-to-severe dry eye disease: a randomised controlled trial protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e048479
Author(s):  
Passara Jongkhajornpong ◽  
Pawin Numthavaj ◽  
Thunyarat Anothaisintawee ◽  
Kaevalin Lekhanont ◽  
Gareth McKay ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Platelet Rich Plasma ◽  
Controlled Trial ◽  
Dry Eye Disease ◽  
Autologous Serum ◽  
Eye Disease ◽  
Eye Drops ◽  
Department Of Ophthalmology ◽  
Autologous Platelet

IntroductionDry eye disease (DED) is a common eye problem. Although the disease is not fatal, it substantially reduces quality of life and creates a high economic burden, especially in patients with moderate-to-severe DED. Several biological tear substitutes (eg, autologous serum (AS), autologous platelet-rich plasma (APRP) and autologous platelet lysate) could effectively improve dry eyes. However, evidence on their comparative efficacy is controversial. This study aims to compare the efficacy of 100% APRP with 100% AS eye drops in patients with moderate-to-severe DED.Methods and analysisThe study is a single-centre, double-blinded randomised, parallel, non-inferiority trial. One hundred and thirty patients with moderate-to-severe DED, aged 18–70 years will be recruited from outpatient clinic, Department of Ophthalmology, Ramathibodi Hospital, Bangkok from February 2021 to January 2023. Patients will be randomised to receive either 100% APRP or 100% AS eye drops (1:1 ratio) for 4 weeks. The primary outcomes are ocular surface disease index (OSDI) and ocular surface staining (OSS) evaluated using the Oxford scale. Secondary outcomes are fluorescein break-up time, Schirmer’s I test, meibomian gland parameters and adverse events. Other measured outcomes include best-corrected visual acuity, intraocular pressure and compliance.Ethics and disseminationThe study protocol and any supplements used in conducting this trial have been approved by the Ethics Committee of Faculty of Medicine, Ramathibodi Hospital, Mahidol University (MURA2020/1930). Informed consent will be obtained from all patients before study entry. Results will be presented in peer-reviewed journals and international conferences.Trial registration numberNCT04683796.

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