An injectable dual-drug-loaded hydrogel for the treatment of bacterial endophthalmitis

Bacterial endophthalmitis is a severe ocular infection that frequently leads to severe visual impairment or blindness. Current clinical treatments primarily rely on intravitreal antibiotics to eliminate pathogens; however, these often fail to control the excessive inflammatory response that contributes to irreversible retinal tissue damage. We developed an injectable thermosensitive hydrogel that treats bacterial endophthalmitis via a combined antibacterial and anti-inflammatory strategy. The hydrogel is constructed with a chitosan/β-glycerophosphate/gelatin platform co-loaded with moxifloxacin and a curcumin-cyclodextrin inclusion complex. In vitro injectability, rheological, and drug release studies demonstrated that the hydrogel precursor rapidly formed a gel following intravitreal injection and enabled sustained drug release. Rheological and swelling-degradation investigations confirmed its low mechanical modulus, minimal swelling capacity, and optimal biodegradation profile, thereby avoiding potential ocular discomfort during intraocular application. This system enables rapid release of moxifloxacin to eliminate bacteria, followed by sustained release of curcumin to mitigate inflammation and reduce inflammatory-mediated tissue injury. Both in vitro and in vivo evaluations demonstrated that the hydrogel showed a strong antibacterial efficacy against S. aureus and significant anti-inflammatory activity, leading to preserved retinal structure and improved visual function. The hydrogel exhibited excellent injectability, biodegradability, and biocompatibility. These properties support its potential for clinical application by providing sustained release of antibacterial and anti-inflammatory drugs for 14 days. To our knowledge, this also represents a novel application of such a dual-drug delivery strategy, specifically for treating S. aureus endophthalmitis. This approach underscores significant promise for future clinical investigation.