Peptide-based nanofiber hydrogels emerge as a transformative platform for advanced ocular drug delivery

Ocular drug delivery faces significant hurdles due to the eye's complex anatomy and physiology, which impede drug pharmacokinetics. Current methods—topical drops, intravitreal injections, and systemic administration—each have limitations, including poor bioavailability, frequent dosing, and systemic side effects. This gap necessitates innovative solutions for effective and sustained drug delivery. Nanofiber hydrogels, particularly self-assembled peptide-based hydrogels, are emerging as a promising platform. Their ability to be precisely tailored for physical and chemical properties, combined with their capacity for controlled drug release and enhanced biocompatibility, positions them as a potential game-changer. Furthermore, their nanofibrous structure can mimic the extracellular matrix, promoting cell adhesion and tissue regeneration.

This comprehensive review synthesizes advancements in nanofiber hydrogels, focusing on self-assembled peptide-based hydrogels and cellulose nanofiber-based hydrogels, for transforming ocular drug delivery. The authors introduce advanced manufacturing techniques capable of precisely modifying hydrogel properties to meet specific therapeutic needs. They elaborate on the distinctive advantages of these hydrogels, including their ability to enhance drug penetration, provide sustained release, and reduce systemic toxicity. The review also delves into therapeutic applications, potential limitations, and future developmental perspectives, drawing insights from preclinical studies across various ophthalmologic conditions.

The review highlights that nanofiber hydrogels, especially those peptide-based, offer significant advantages for ocular drug delivery. They can be precisely tailored to exhibit specific physical and chemical properties, enabling highly controlled release of therapeutic agents and enhancing biocompatibility within the ocular environment. Their unique nanofibrous structure effectively mimics the extracellular matrix, which is crucial for promoting cell adhesion and facilitating tissue regeneration in damaged ocular tissues.

Preclinical studies have validated the efficacy of these hydrogels in treating a range of ophthalmologic conditions, including age-related macular degeneration, bacterial keratitis, ocular alkali burns, and non-infectious uveitis.

These systems demonstrate an ability to enhance drug penetration into ocular tissues, provide sustained drug release over extended periods, and significantly reduce systemic toxicity compared to conventional administration routes. However, the review also identifies challenges in translating these promising laboratory findings into widespread clinical applications, citing species-specific responses, the inherent complexity of human biology, and the need for rigorous safety assessments as primary hurdles.