Frozen reinforced microneedles loaded with NIR-photothermal nanozyme for keratitis treatment

Developing a potential alternative with safe, minimally invasive, and highly effective antimicrobial properties is significant for treating bacterial keratitis. In this paper, we present novel nanozyme-loaded frozen reinforced microneedles (FR-MNs) with the ability to deliver the nanozyme controllably inside the cornea to treat keratitis. The nanozymes constructed by the iron ion, tannic acid (TA), and poly (vinylpyrrolidone; PVP) (FeTAP) are incorporated within the MNs tips. The freezing process could greatly enhance the mechanical strength of the tips. Taking advantage of the pH-dependent peroxidase-mimetic activities of FeTAP, the FeTAP integrated MNs can catalyze hydrogen peroxide (H2O2) to produce much more oxidative hydroxyl (•OH) in acidic condition to kill bacteria. Meanwhile, the excellent photothermal efficiency of FeTAP can further enhance the ability of bacterial killing under near-infrared (NIR) irradiation. In addition, the photothermal action can rapidly increase the temperature of the frozen microneedles and subsequently soften the MNs after penetration, which can result in better adaptation of MNs to soft tissues. Based on the nanozyme-loaded FR-MNs, we have demonstrated that this formulation exhibited superior therapeutic potential in the rat eye infection model compared with conventional eye drops. These features impart the proposed nanozyme-loaded FR-MNs with great scientific value and promising clinical applications.