Construction of graphene quantum dot-based dissolving microneedle patches for the treatment of bacterial keratitis.

ABSTRACT

Bacterial keratitis (BK) is an ophthalmic infection caused by bacteria and poses a risk of blindness. Numerous drugs have been used to treat BK, the majority suffered from limited effect owing to their backward antimicrobial and delivery efficacy. Herein, we evaluated the antibacterial effect of a cationic carbon-based nanomaterial, i.e., imidazole-modified graphene quantum dots (IMZ-GQDs), which exhibits disinfection rates of >90% against three typical Gram-positive strains within 3 h owing to the loss of membrane integrity and decline in membrane potential. For ocular application, we further developed IMZ-GQDs-loaded dissolving microneedle patches (IMZ-GQDs MNs) via a typical two-step micromolding method. IMZ-GQDs MNs showed sufficient dissolution and penetration for intrastromal delivery in vitro and successfully overcome the rabbit corneal epithelial layer in vivo. The excellent biocompatibility of IMZ-GQDs MNs was demonstrated both in cell and animal models, and they exhibited low cytotoxicity, low invasiveness and low ocular irritation. The topical application of IMZ-GQDs MNs has the benefits of both high antibacterial activity and effective drug delivery, thereby leading to the resolution of Staphylococcus aureus-induced BK in rabbits in 7 days. Therefore, IMZ-GQDs MNs is a promising approach for BK treatment, which is safe and efficient.