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Published on: April 7, 2014
Inflammation-responsive molecular-gated contact lens for the treatment of corneal neovascularization
Rong Sun1, Shuting Ma1, Xi Chen1
1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, PR China.
Abstract:
Corneal neovascularization (CNV) badly damages the corneal transparency, resulting in visual disturbance and blindness. The frequent administration of glucocorticoid eye drops in clinical increases the possibility of side effects and reduces patient compliance. Considering CNV is often accompanied by an increase in ROS production, a ROS-responsive monomer 2-(methylthio)ethyl methacrylate was introduced into the matrix as a "gating switch". The prepared dexamethasone contact lenses (MCLs@Dex) showed a significant H2O2-responsive release for 168 h. To avoid corneal hypoxia and neovascularization caused by long-term wearing, high‑oxygen-permeability fluorosiloxane materials were incorporated. The oxygen permeability of MCLs@Dex was 4 times that of commercially available hydrogel contact lenses and had ultra-low protein adsorption, which meets the requirements of long-term wearing. In vivo pharmacokinetic studies showed that MCLs@Dex increased the mean residence time by 19.7 times and bioavailability by 2.29 times compared with eye drops, validating the ROS response and sustained release properties. More importantly, MCLs@Dex had satisfactory effects on reducing inflammation and decreasing the related cytokines and oxidative stress levels, and demonstrated significant inhibition of neovascularization, with a suppression rate of 76.53% on the 14th day. This responsive drug delivery system provides a promising new method for the safe and effective treatment of ocular surface diseases.
Insights
New dexamethasone contact lenses (MCLs@Dex) offer a promising treatment for corneal neovascularization (CNV). These responsive lenses provide sustained drug delivery, reducing inflammation and inhibiting CNV by over 76%.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Drug Delivery Systems
Background:
- Corneal neovascularization (CNV) impairs vision and can lead to blindness.
- Current treatments like glucocorticoid eye drops have limitations including side effects and poor patient compliance.
- CNV is associated with increased reactive oxygen species (ROS) production.
Purpose of the Study:
- To develop novel dexamethasone-loaded contact lenses (MCLs@Dex) for sustained and responsive drug delivery.
- To investigate the potential of ROS-responsive materials for treating CNV.
- To evaluate the efficacy and safety of MCLs@Dex for long-term ocular surface disease management.
Main Methods:
- Fabrication of dexamethasone-loaded contact lenses using ROS-responsive monomers and high-oxygen-permeability fluorosiloxane materials.
- In vitro assessment of hydrogen peroxide (H2O2)-responsive drug release over 168 hours.
- In vivo pharmacokinetic studies comparing MCLs@Dex to eye drops.
- Evaluation of anti-inflammatory and anti-neovascularization effects in an animal model.
Main Results:
- MCLs@Dex exhibited significant H2O2-responsive dexamethasone release for 168 hours.
- The lenses demonstrated superior oxygen permeability and ultra-low protein adsorption, suitable for long-term wear.
- In vivo studies showed a 19.7-fold increase in mean residence time and 2.29-fold increase in bioavailability compared to eye drops.
- MCLs@Dex significantly reduced inflammation, oxidative stress, and inhibited neovascularization by 76.53% on day 14.
Conclusions:
- MCLs@Dex represent a safe and effective ROS-responsive drug delivery system for treating corneal neovascularization.
- This novel contact lens platform offers sustained drug release and improved therapeutic outcomes for ocular surface diseases.
- The developed system overcomes limitations of conventional eye drops, enhancing patient compliance and treatment efficacy.
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