Matrix Metalloproteinase 9 and Transglutaminase 2 Expression at the Ocular Surface in Patients with Different Forms of Dry Eye Disease

Ophthalmology ◽  
2015 ◽  
Vol 122 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Pasquale Aragona ◽  
M'Hammed Aguennouz ◽  
Laura Rania ◽  
Elisa Postorino ◽  
Margherita Serena Sommario ◽  
...  
Ophthalmology ◽  
2016 ◽  
Vol 123 (11) ◽  
pp. 2300-2308 ◽  
Author(s):  
Elisabeth M. Messmer ◽  
Victoria von Lindenfels ◽  
Alexandra Garbe ◽  
Anselm Kampik

2020 ◽  
Vol 10 (03) ◽  
pp. 211-219
Author(s):  
Diaz-Llopis Manuel ◽  
Pinazo-Duran Maria Dolores ◽  
Diaz-Guiñon Loreto ◽  
Rahhal-Ortuño Miriam ◽  
Gallego-Pinazo Roberto ◽  
...  

2021 ◽  
Vol 13 ◽  
pp. 251584142110127
Author(s):  
Preeya K. Gupta ◽  
Nandini Venkateswaran

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.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 905
Author(s):  
Sangeeta Kumari ◽  
Madhuri Dandamudi ◽  
Sweta Rani ◽  
Elke Behaeghel ◽  
Gautam Behl ◽  
...  

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.


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