Besifloxacin-eluting contact lens with sustained drug delivery and enhanced bioavailability

Bacterial keratitis is a prevalent and sight-threatening ocular infection. Current treatments typically involve intensive antibiotic eye drops or ointments; however, their effectiveness is limited by poor corneal penetration, low bioavailability, and suboptimal patient adherence. These limitations are particularly pronounced for besifloxacin, a fourth-generation fluoroquinolone with broad-spectrum antibacterial activity but low octanol-water partition coefficient and poor aqueous solubility. Here, we present a besifloxacin-eluting contact lens (BXF-CL) engineered to enhance corneal drug penetration and sustain therapeutic antibiotic levels. BXF-CLs were fabricated by encapsulating a thin, drug-loaded polymer film-composed of physiologically inert polymers (ethylcellulose and Eudragit® RSPO)-within the periphery of soft contact lenses <i>via</i> UV polymerization. The resulting lenses showed key physical properties comparable to commercial contact lenses, including morphology, water content, and light transmittance. <i>In vitro</i> and <i>in vivo</i> studies demonstrated sustained antibiotic release at clinically relevant levels for over 24 h. Furthermore, BXF-CLs maintained stable drug release and lens properties following terminal sterilization and two years of storage. Pharmacokinetic studies in rabbits revealed markedly enhanced intraocular delivery, achieving up to a 21.6-fold higher peak concentration in the aqueous humor compared with hourly besifloxacin eye drops. The eluted drug retained potent antimicrobial activity against both Gram-positive (<i>Staphylococcus aureus</i>) and Gram-negative (<i>Escherichia coli</i>) bacteria in agar disk diffusion assays. Biocompatibility was confirmed by <i>in vitro</i> cytotoxicity and <i>in vivo</i> ocular irritation tests. Collectively, these results identify BXF-CL as a promising platform for sustained topical antibiotic delivery and improved management of bacterial keratitis.