Surface modification of commercial intraocular lens by zwitterionic and antibiotic-loaded coating for preventing postoperative endophthalmitis

Abstract

After cataract surgery, to prevent possible postoperative endophthalmitis (POE) caused by attached pathogenic bacteria onto the surface of implanted intraocular lens (IOL), various antibiotic-loaded IOLs have been proposed and widely studied to inhibit bacterial infection. However, most of these developed antibiotic-loaded IOLs still suffer from shortcomings such as insufficient drug loading, short release time, poor biocompatibility, and risk of secondary infection. Herein, we propose a zwitterionic and high-drug loading coating for surface modification of commercial hydrophobic IOL with both antifouling and antibacterial properties to effectively prevent POE. In this strategy, zwitterionic poly(carboxylbetaine-co-dopamine methacrylamide) copolymers (pCBDA) and dopamine (DA) were first robustly co-deposited onto IOL surface via facile mussel-inspired chemistry, resulting in a hydrophilic coating (defined as PCB) without sacrificing the high light transmittance of the native IOL. Subsequently, amikacin (AMK), an amine-rich antibiotic was reversibly conjugated onto the coating through the acid-sensitive Schiff base bonds formed by the reaction between amino and catechol groups, with high-drug payload over ∼35.5 μg per IOL and 30 days of sustained drug release under weak acid environment. Benefiting from the antifouling property of zwitterionic pCBDA copolymers, the intraocularly implanted PCB/AMK-coated IOL could effectively resist the adhesion and proliferation of residual LECs to inhibit the development of posterior capsule opacification (PCO) without affecting the normal ocular tissues, demonstrating excellent in vivo biocompatibility. Moreover, the synergy of zwitterionic pCBDA and conjugated AMK with acidic-dependent release behavior endowed this PCB/AMK-coated IOL strong antibacterial activity against both in vitro biofilm formation and in vivo postoperative Staphylococcus aureus infection, suggesting its promising application in preventing POE.