Personalized curved-backing microneedles with amphotericin B-loaded nanoparticles for fungal keratitis treatment

Fungal keratitis (FK) is a severe ocular infection that often leads to vision impairment, yet its clinical management remains challenging due to poor drug bioavailability from conventional eye drops and tissue damage risks associated with intraocular injections. Microneedles (MNs) offer a minimally invasive alternative for corneal drug delivery, but conventional designs cause pain, structural damage, and reduced corneal transparency. Herein, we report a finite element simulation-assisted strategy to fabricate personalized curved-backing microneedles with a curvature-matched backing that ensures conformal surface contact, controlled penetration depth, and uniform drug distribution, effectively overcoming the limitations of conventional MNs. To enhance drug delivery, amphotericin B, a hydrophobic antifungal agent, was encapsulated in poly(lactic acid) nanoparticles, achieving improved solubility and sustained release. In vitro and in vivo short-term evaluations demonstrated that this integrated system effectively inhibited C. albicans growth and promoted corneal repair in a rabbit model of FK, without inducing significant ocular irritation or structural damage over the 14-day observation period. Our design strategy offers a viable approach to addressing barriers associated with corneal drug delivery.