Emerging Ocular-Surface Antimicrobial Delivery Strategies for Infectious Keratitis

Infectious keratitis remains a leading cause of corneal blindness worldwide despite effective antimicrobial agents. Conventional topical therapy is limited by rapid precorneal clearance, restricted corneal penetration, and inadequate stromal drug exposure, resulting in subtherapeutic drug concentrations. These pharmacokinetic barriers are particularly important in fungal, protozoal, deep stromal, and antimicrobial-resistant keratitis, where prolonged or targeted exposure is essential for successful treatment. This review evaluates emerging ocular antimicrobial delivery strategies through a pharmacokinetic framework, emphasizing the relationship among delivery platform, depth of corneal involvement, pathogen-specific requirements, and clinical feasibility.

We searched PubMed and Scopus for literature published from 2017 through August 31, 2026, including preclinical studies, clinical trials, and regulatory records. Platforms covered include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers, hybrid nanocarriers, mucoadhesive formulations, hydrogels, drug-eluting contact lenses, ocular inserts, microneedles, intrastromal delivery, photoactivated chromophore for keratitis corneal cross-linking (PACK-CXL), and amniotic membrane. Quantitative pharmacokinetic outcomes were compared with those of conventional formulations.

Each platform addresses a distinct pharmacokinetic challenges, so platforms function as complementary options. Quantitative pharmacokinetic data are compared to assess improvements in ocular residence, corneal exposure, and sustained drug delivery relative to conventional formulations. A decision-tree framework is proposed to guide platform selection by drug lipophilicity, corneal permeability, and dosing requirements. Newer systemic anti-infective agents with potential for ocular reformulation are also identified. Hybrid systems increasingly target multiple limitations simultaneously, but most evidence remains preclinical, and human corneal pharmacokinetic data are limited.

Future studies should prioritize direct comparisons of novel platforms with standard therapy and establish whether improved delivery maintains concentrations above pathogen-specific inhibitory thresholds and translates into superior clinical outcomes.