Methotrexate-Loaded Liposomal Formulation Enables 6-Week Sustained Intraocular Therapeutic Drug Release in a Porcine...

Area of Science:

• Ophthalmology
• Drug Delivery Systems
• Nanotechnology

Background:

• Methotrexate (MTX) is crucial for treating ocular diseases but requires frequent intravitreal injections due to its short half-life.
• Existing sustained-release systems, like PLGA implants, necessitate invasive surgery, increasing complication risks.
• Current delivery methods limit practical application and patient compliance for chronic ocular conditions.

Purpose of the Study:

• To develop and evaluate a novel liposomal formulation of methotrexate for sustained intravitreal delivery.
• To overcome the limitations of frequent injections and invasive implantation associated with current MTX therapies.
• To provide a clinically and surgically optimized drug delivery system for intraocular diseases.

Main Methods:

• MTX-loaded liposomes were formulated using phospholipids for intravitreal administration via a 30-gauge cannula.
• Sustained drug release was assessed in vitro and in vivo in a large animal pig model.
• Biocompatibility was evaluated using optical coherence tomography (OCT) for retinal structure and electroretinography (ERG) for retinal function.

Main Results:

• The liposomal formulation achieved sustained methotrexate release at therapeutic levels for over six weeks post-injection.
• In vivo studies in a pig model confirmed prolonged drug delivery and efficacy.
• Retinal structure and function remained stable, indicating high biocompatibility of the liposomal formulation.

Conclusions:

• MTX-loaded liposomes offer a promising, minimally invasive alternative for sustained ocular drug delivery.
• This novel formulation overcomes the limitations of frequent injections and surgical implantation.
• The liposomal system provides a clinically optimized approach for managing intraocular lymphoma and proliferative vitreoretinopathy.