Surface Self-Assembly Construction of Therapeutic Contact Lens with Bacterial "Kill-Releasing" and Drug-Reloading Capabilities for Efficient Bacterial Keratitis Treatment.

Abstract

Bacterial keratitis, an ophthalmic emergency, can cause corneal perforation and even endophthalmitis, thus leading to severe visual impairment. To achieve effective treatment of bacterial keratitis, good bioavailability of antimicrobial drugs on the ocular surface is desired. In this investigation, a layer-by-layer (LBL) self-assembly combined with the host-guest recognition was used to construct an antibacterial coating on the surface of corneal contact lens (CLs) to improve drug bioavailability and achieve successful treatment of bacterial keratitis. First, a radical copolymerization of acrylic acid (AA) and 1-adamantan-1-ylmethyl acrylate (AdA) was carried out to synthesize a polyanionic copolymer P(AA-co-AdA) (defined as PAcA). Then, PAcA copolymer combined with poly(ethyleneimine) (PEI) was used for a layer-by-layer (LBL) self-assembly to fabricate multilayer films on the surface of CLs. An antibacterial conjugate, β-cyclodextrin-levofloxacin (β-CD-LEV), was successfully synthesized and utilized to generate antibacterial coating through a host-guest interaction between AdA and β-CD-LEV. The antibacterial ability and treatment effect of bacterial keratitis was evaluated by in vitro assay and in vivo test in an animal model of staphylococcal keratitis, demonstrating that the antibacterial coating had good antibacterial and germicidal efficacy both in vivo and in vitro. We believe that this work will provide a promising strategy for the treatment of bacterial keratitis.