Innovative Polymeric Micelles with In-Situ Gelation for Enhanced Ocular Delivery of Ketoconazole

Purpose

This study aims to develop and evaluate a micellar in situ gel formulation of ketoconazole for ocular drug delivery, to enhance solubility, prolong retention time, and improve therapeutic efficacy against fungal eye infections.

Methods

A micellar-based, ion-sensitive in situ gel system was prepared using the solvent evaporation technique. The micelles were formed by incorporating Pluronic F127 and chitosan for ketoconazole solubilization, and sodium alginate was added to impart ion sensitivity. The micellar system was optimized using a central composite design and evaluated for particle size, surface morphology, and drug entrapment efficiency. The in-situ gel was characterized for its appearance, gelation capacity, pH, viscosity, drug content, in vitro release, sterility, and stability.

Results

The optimized formulation exhibited an average particle size of 161.1 ± 2.4 nm with uniform dispersion, and a zeta potential of + 11.7 ± 0.4 mV, indicating favorable stability and bioadhesion. The entrapment efficiency was 81.44 ± 3.6%, indicating effective solubilization of ketoconazole within the micellar core. The in vitro release study demonstrated a sustained release profile, with 91 ± 2.4% of the drug released over 12 h. The in-situ gel exhibited prolonged stability for 30 days, good ocular tolerance, and extended drug retention time.

Conclusion

The ketoconazole-loaded micellar in situ gel formulation represents a promising approach for ocular drug delivery, offering sustained drug release and enhanced therapeutic efficacy. This formulation has the potential to improve patient compliance by reducing dosing frequency and enhancing ocular bioavailability, ultimately providing an effective treatment for fungal eye infections.