ROS-Responsive Cationic Nanoparticles for Cyclosporine A Delivery in Dry Eye Disease: A Dual-Functional...

Area of Science:

• Ophthalmology
• Nanotechnology
• Biomaterials

Background:

• Dry eye disease (DED) affects 10-30% globally, driven by oxidative stress and inflammation.
• Current treatments like cyclosporine A (CsA) have limitations including poor solubility and targeted delivery.
• Reactive oxygen species (ROS) exacerbate DED by damaging corneal epithelium.

Purpose of the Study:

• To develop novel ROS-responsive cationic nanoparticles for targeted CsA delivery in DED.
• To enhance ocular retention and therapeutic efficacy of CsA for DED treatment.
• To evaluate the safety and effectiveness of the developed nanoplatform in a DED mouse model.

Main Methods:

• Coassembly of CsA with a cationic amphiphilic copolymer P-(MS-a-EG) to form ROS-responsive nanoparticles (CsA@P-(MS-a-EG) NPs).
• Evaluation of nanoparticle properties including ROS-triggered release and ocular surface adhesion.
• Assessment of therapeutic effects in a DED mice model, including tear secretion, tear film stability, and corneal healing.
• In vivo biosafety evaluation to determine systemic toxicity.

Main Results:

• CsA@P-(MS-a-EG) NPs demonstrated enhanced ocular retention via electrostatic interactions.
• The nanoparticles effectively restored tear secretion and improved tear film stability in DED mice.
• Corneal epithelium thickness was normalized, indicating accelerated healing.
• No systemic toxicity was observed, confirming excellent biosafety.

Conclusions:

• The developed CsA-loaded cationic nanoparticles offer a dual-functional platform for DED therapy.
• ROS-responsive release and corneal adhesion properties enhance therapeutic outcomes.
• This nanoplatform presents a targeted, patient-friendly, and safe strategy for managing DED.