Work

Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis

Year: 2025

Type: article

Abstract: Fungal keratitis (FK) is a challenging-to-manage blinding corneal infectious disease that often leads to severe sequelae, such as corneal leukoplakia regardless of curative care. Moreover, the unique anatomical structure and tear turnover of the eye significantly limit the bioavailability and therapeutic efficacy of traditional eye drops. Inspired by the unique pathological features of corneal ulcers, we report a thermosensitive multifunctional eye drop, designated PX-TA, based on a poloxamer (PX) and a collagen-adhesive tannic acid (TA), for prolonged and efficient treatment of FK. PX-TA transforms into a gel at body temperature and adheres to exposed collagen at the ulcer site; this significantly improves the corneal retention time and bioavailability. PX-TA maintains corneal retention for at least 90 min, substantially exceeding both the 15-min limit of commercial mucoadhesive eye drops and the 30-min threshold of conventional in situ gels. When loaded with amphotericin B (AmB), once-daily PX-TA-AmB administration effectively suppresses inflammation and corneal scarring, demonstrating superior efficacy over six-times-daily free AmB drops and a good safety profile. Mechanistic investigations reveal that PX-TA-AmB mediates its therapeutic effects through the MAPK6/PI3K/AKT signaling pathway. Moreover, the metal-chelating properties of TA inhibit the copper-dependent enzyme lysyl oxidase (LOX), resulting in reduced matrix fibrosis. Overall, the use of PX-TA-AmB drops represents a simplified yet effective strategy for the potential clinical management of FK, inspiring the design of eye drop formulations. • Collagen-binding Design: Engineered tannic acid-based thermosensitive ophthalmic formulation targeting exposed collagen in fungal corneal ulcers. • Enhanced Retention: Achieved sustained corneal surface retention (>90 min) vs conventional formulations (15 min), enabling once-daily use. • Multifunctional Therapeutic Platform: Integrated antifungal, anti-inflammatory, and anti-fibrotic properties in thermosensitive eye drops. • Dual Mechanisms: Therapeutic effects mediated through MAPK6/PI3K/AKT pathway modulation and tannic acid metal-chelating properties.

Source: Bioactive Materials

DOI: 10.1016/j.bioactmat.2025.04.011