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 via UV polymerization. The resulting lenses showed key physical properties comparable to commercial contact lenses, including morphology, water content, and light transmittance. In vitro and in vivo 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 (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria in agar disk diffusion assays. Biocompatibility was confirmed by in vitro cytotoxicity and in vivo ocular irritation tests. Collectively, these results identify BXF-CL as a promising platform for sustained topical antibiotic delivery and improved management of bacterial keratitis.