Preclinical Efficacy, Tolerability, and Exploratory Model-Based Pharmacokinetics of a Dual-Drug Biodegradable Intracameral Implant in Rabbits

Background/Objectives: Postoperative management after cataract surgery involves topical anti-inflammatory and antimicrobial treatments, whose clinical performance may be affected by adherence, administration technique, and intraocular exposure. This study evaluated a biodegradable poly(lactic-co-glycolic acid) intracameral implant containing moxifloxacin hydrochloride and dexamethasone, designed for intraoperative placement. Methods: Clinical tolerability, anti-inflammatory activity in a uveitis model, and antibacterial performance following a low-inoculum intravitreal challenge with Pseudomonas aeruginosa were evaluated in New Zealand White rabbits. Aqueous humor pharmacokinetic profiles were also assessed in phakic and aphakic eyes. Clinical follow-up included slit-lamp biomicroscopy and intraocular pressure measurements. Concentration–time data were analyzed by means of nonlinear mixed-effects models and model-based simulations. Results: No visible implant material remained four weeks after insertion. A transient pseudo-membrane was observed shortly after implantation in some implanted eyes, but it resolved spontaneously and was not accompanied by clinical inflammatory signs. No sustained increase in intraocular pressure was observed during follow-up. Untreated bacterially challenged eyes rapidly developed severe endophthalmitis, whereas implant-treated eyes showed no clinical evidence of endophthalmitis. In the exploratory uveitis experiment, implant-treated eyes showed lower clinical inflammatory scores and faster recovery than matched eyes without the implant. Model-based simulations suggested persistent dexamethasone exposure through day 30, whereas moxifloxacin reached an early peak and was predominantly below the limit of quantification from day 7 onward. Conclusions: These findings provide preliminary preclinical proof-of-concept evidence supporting the clinical tolerability and pharmacological activity of the implant under the experimental conditions evaluated. The results are hypothesis-generating, should not be extrapolated to clinical safety or efficacy, and do not demonstrate microbiological eradication. Further studies with larger cohorts, pseudophakic models, microbiological and histopathological endpoints, and optimized pharmacokinetic sampling are required.