Hybrid polymeric nanomicelles for ocular delivery of ofloxacin: formulation optimization, release mechanism, and transcorneal permeation

Abstract

Bacterial infections of the anterior segment of the eye remain difficult to manage due to rapid precorneal clearance, limited corneal permeability, and short residence time associated with conventional ophthalmic formulations. These challenges often necessitate frequent dosing, which may reduce patient adherence and therapeutic efficiency. Ofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly used for ocular infections; however, its topical effectiveness is limited by poor corneal penetration and low ocular bioavailability. Therefore, this study aimed to develop and characterize ofloxacin-loaded hybrid polymeric nanomicelles based on D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and Poloxamer 188 (P188) and to evaluate their in vitro release profile and ex vivo transcorneal permeation as a strategy to improve the topical ocular delivery potential of ofloxacin. Ofloxacin-loaded nanomicelles were prepared using TPGS and P188 via the thin-film hydration technique. The effect of polymer composition on micellar characteristics, drug encapsulation, release behavior, and corneal permeation was systematically evaluated. The optimized formulation (F8), composed of 30 mg TPGS and 20 mg P188, exhibited a small particle size (14.61 ± 0.06 nm), narrow size distribution (polydispersity index [PDI], 0.158 ± 0.02), mildly negative zeta potential (−6.47 ± 0.4 mV), and high entrapment efficiency (88.7 ± 0.92%). In vitro release studies showed a sustained release profile, with approximately 80% drug release over 10 h, compared with less than 25% from the pure ofloxacin suspension. Ex vivo transcorneal permeation studies using excised sheep cornea demonstrated significantly enhanced drug transport, characterized by increased steady-state flux and reduced lag time. Overall, the findings indicate that hybrid polymeric nanomicelles represent a promising platform for improving the biopharmaceutical performance and corneal transport of topical ofloxacin eye drops. In vivo ocular residence time and clinical antibacterial efficacy were not assessed in this study and should be explored in future investigations. Graphical abstract :