scholarly journals Development of Lactoferrin-Loaded Liposomes for the Management of Dry Eye Disease and Ocular Inflammation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1698
Author(s):  
Ana López-Machado ◽  
Natalia Díaz-Garrido ◽  
Amanda Cano ◽  
Marta Espina ◽  
Josefa Badia ◽  
...  

Dry eye disease (DED) is a high prevalent multifactorial disease characterized by a lack of homeostasis of the tear film which causes ocular surface inflammation, soreness, and visual disturbance. Conventional ophthalmic treatments present limitations such as low bioavailability and side effects. Lactoferrin (LF) constitutes a promising therapeutic tool, but its poor aqueous stability and high nasolacrimal duct drainage hinder its potential efficacy. In this study, we incorporate lactoferrin into hyaluronic acid coated liposomes by the lipid film method, followed by high pressure homogenization. Pharmacokinetic and pharmacodynamic profiles were evaluated in vitro and ex vivo. Cytotoxicity and ocular tolerance were assayed both in vitro and in vivo using New Zealand rabbits, as well as dry eye and anti-inflammatory treatments. LF loaded liposomes showed an average size of 90 nm, monomodal population, positive surface charge and a high molecular weight protein encapsulation of 53%. Biopharmaceutical behaviour was enhanced by the nanocarrier, and any cytotoxic effect was studied in human corneal epithelial cells. Developed liposomes revealed the ability to reverse dry eye symptoms and possess anti-inflammatory efficacy, without inducing ocular irritation. Hence, lactoferrin loaded liposomes could offer an innovative nanotechnological tool as suitable approach in the treatment of DED.

2019 ◽  
Vol 17 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Agnė Žiniauskaitė ◽  
Symantas Ragauskas ◽  
Anita K. Ghosh ◽  
Rubina Thapa ◽  
Anne E. Roessler ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2139
Author(s):  
Rita Mencucci ◽  
Giovanni Strazzabosco ◽  
Virginia Cristofori ◽  
Andrea Alogna ◽  
Daria Bortolotti ◽  
...  

This study aimed to evaluate the mucoadhesive and regenerative properties of a novel lubricating multimolecular ophthalmic solution (GlicoPro®) extracted from snail mucus and its potential anti-inflammatory and analgesic role in the management of dry eye disease (DED). GlicoPro bio-adhesive efficacy was assessed using a lectin-based assay, and its regenerative properties were studied in a human corneal epithelial cell line. In vitro DED was induced in human corneal tissues; the histology and mRNA expression of selected genes of inflammatory and corneal damage biomarkers were analyzed in DED tissues treated with GlicoPro. A higher percentage of bio-adhesivity was observed in corneal cells treated with GlicoPro than with sodium hyaluronate-based compounds. In the scratch test GlicoPro improved in vitro corneal wound healing. Histo-morphological analysis revealed restoration of cellular organization of the corneal epithelium, microvilli, and mucin network in DED corneal tissues treated with GlicoPro. A significant reduction in inflammatory and ocular damage biomarkers was observed. High-performance liquid chromatography-mass spectrometry analysis identified an endogenous opioid, opiorphin, in the peptide fraction of GlicoPro. In conclusion, GlicoPro induced regeneration and bio-adhesivity in corneal cells; moreover, considering its anti-inflammatory and analgesic properties, this novel ophthalmic lubricating solution may be an innovative approach for the management of DED.


2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Bongkyun Park ◽  
Tae Gu Lee ◽  
Soo‐Wang Hyun ◽  
Kyuhyung Jo ◽  
Ik Soo Lee ◽  
...  
Keyword(s):  
Dry Eye ◽  

2021 ◽  
Vol 22 (22) ◽  
pp. 12102
Author(s):  
Md. Mahbubur Rahman ◽  
Dong Hyun Kim ◽  
Chul-Kyu Park ◽  
Yong Ho Kim

Dry eye disease (DED) is one of the major ophthalmological healthcare challenges worldwide. DED is a multifactorial disease characterized by a loss of homeostasis of the tear film, and its main pathogenesis is chronic ocular surface inflammation related with various cellular and molecular signaling cascades. The animal model is a reliable and effective tool for understanding the various pathological mechanisms and molecular cascades in DED. Considerable experimental research has focused on developing new strategies for the prevention and treatment of DED. Several experimental models of DED have been developed, and different animal species such as rats, mice, rabbits, dogs, and primates have been used for these models. Although the basic mechanisms of DED in animals are nearly identical to those in humans, proper knowledge about the induction of animal models is necessary to obtain better and more reliable results. Various experimental models (in vitro and in vivo DED models) were briefly discussed in this review, along with pathologic features, analytical approaches, and common measurements, which will help investigators to use the appropriate cell lines, animal, methods, and evaluation parameters depending on their study design.


2019 ◽  
Vol 11 ◽  
pp. 251584141987036 ◽  
Author(s):  
Stacy L. Haber ◽  
Vera Benson ◽  
Casey J. Buckway ◽  
Jennifer M. Gonzales ◽  
David Romanet ◽  
...  

The objective of this article is to review the pharmacology, efficacy, and safety of lifitegrast and determine its role relative to other agents in the management of dry eye disease. A PubMed search (1946 to December 2018) using the terms lifitegrast and SAR 1118 was conducted to identify relevant articles. In vitro or in vivo evaluations of lifitegrast published in the English language were eligible for inclusion. Phase II and III trials were selected for review of efficacy and safety. Four randomized controlled trials evaluated the efficacy and safety of lifitegrast 0.5% ophthalmic solution for 12 weeks, and 1 additional trial assessed safety for 1 year. In a majority of the trials, lifitegrast caused statistically significant improvements in inferior corneal fluorescein staining scores and eye dryness scores. The most common adverse effects were eye irritation, dysgeusia, and reduced visual acuity, and most were mild to moderate in severity. Lifitegrast has a novel mechanism of action and is safe and effective for the treatment of dry eye disease. At this time, lifitegrast may be considered as an option for patients who have an inadequate response to artificial tears.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2792 ◽  
Author(s):  
Bongkyun Park ◽  
Kyuhyung Jo ◽  
Tae Gu Lee ◽  
Soo-Wang Hyun ◽  
Jin Sook Kim ◽  
...  

Polydatin (also named pieceid, (E)-piceid, (E)-polydatin, trans-polydatin, or 3,5,4’-trihydroxystilbene-3-b-D-glucoside) is a monocrystalline compound isolated from the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae). A previous study showed that polydatin has antioxidant and anti-inflammatory effects. However, the effect of polydatin in dry eye disease (DED) has not been elucidated. DED rat models were induced by exorbital lacrimal gland-excision. In vivo, the present study showed that the excision of lacrimal glands induced changes such as reduced tear fluid, severe corneal irregularity, damage, tear film break, and goblet cell loss as well as increased inflammation cytokine and NLRP3 expression in conjunctival tissue. However, these changes were restored by polydatin eye dropping. In vitro, polydatin inhibited hyperosmolar stress-induced inflammation through attenuation of the translocation of NF-κB to the nucleus and the mRNA expression of TNF-α, IL-6, IL-1β, and MMP9. In addition, the hyperosmolar stress-induced NLRP3 inflammasome pathway and ROS production were inhibited by polydatin. Our findings provided insight into the effect of polydatin as a candidate reagent for the treatment of DED.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 190
Author(s):  
Gaia Favero ◽  
Enrico Moretti ◽  
Kristína Krajčíková ◽  
Vladimíra Tomečková ◽  
Rita Rezzani

Dry eye disease is a multifactorial pathology compromising the quality of life of patients, resulting in significant damage of the ocular surface and discomfort. The current therapeutical strategies are not able to definitively resolve the underlying causes and stop the symptoms. Polyphenols are promising natural molecules that are receiving increasing attention for their activity/effects in counteracting the main pathologic mechanisms of dry eye disease and reducing its symptoms. In the present review, a deep literature search focusing on the main polyphenols tested against dry eye disease was conducted, analyzing related in vitro, in vivo, and clinical studies to provide a comprehensive and current review on the state of the art. Polyphenols present multiple effects against dry eye diseases-related ocular surface injury. In particular, the observed beneficial effects of polyphenols on corneal cells are the reduction of the pathological processes of inflammation, oxidative stress, and apoptosis and modulation of the tear film. Due to numerous studies reporting that polyphenols are effective and safe for treating the pathological mechanisms of this ocular surface disease, we believe that future studies should confirm and extend the evidence of polyphenols efficacy in clinical practice against dry eye disease and help to develop new ophthalmic drug(s).


2019 ◽  
Vol 12 (3) ◽  
pp. 75-82
Author(s):  
Inna A. Riks

This literature review focuses on the need for anti-inflammatory therapy for dry eye disease (DED). Causes of development and mechanisms of pathogenesis of DED are presented. Principles of action of various groups of anti-inflammatory medications, as well as recommendations for cyclosporine use of are described. The results of studies on cyclosporine efficacy are highlighted, principles of cyclosporin prescription in DED are listed.


2019 ◽  
Vol 4 (1) ◽  
pp. e000315
Author(s):  
Penny Asbell ◽  
Elisabeth Messmer ◽  
Colin Chan ◽  
Gary Johnson ◽  
Brigitte Sloesen ◽  
...  

ObjectiveDry eye disease is a multifactorial chronic disease, leading to ocular discomfort and visual disturbance with a substantial impact on quality of life. Therefore, the patient’s perspective should be taken into account early in the drug development process. We have developed a step-by-step methodology based on the self-explicated conjoint approach to assess the needs and preferences of patients with moderate-to-severe dry eye disease.Methods and AnalysisFollowing a literature review and social media listening (step 0), qualitative phone call interviews were conducted with 12 patients (step 1). Patients’ responses underwent content analysis and were coded, quantified and displayed as charts. Based on the emerging trends and attributes identified as relevant in steps 0 and 1, a quantitative online questionnaire was designed and conducted with 160 patients across four countries (step 2).ResultsThe online questionnaire was rated as easy/very easy to understand by 60% of respondents, 62% rated the survey as easy/very easy to complete and 71% rated it as interesting/very interesting. Treatment satisfaction was the most important aspect for patients, and the three most relevant attributes were as follows (with the most important indexed to 100%): ‘treatment effectiveness on symptoms of dry eyes’ (100%), ‘frequency of treatment use’ (96%) and ‘how the treatment works’ (95%).ConclusionOur methodology was well received by patients, and the results will help inform future clinical trial development and discussions with health technology assessment bodies and regulators on unmet needs and product attributes that are of most value to patients with dry eye disease.


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