Introduction: The delivery of antiviral agents to ocular tissues presents a significant challenge due to rapid drug clearance and limited bioavailability. Ganciclovir, a potent antiviral drug used for treating viral eye infections, suffers from poor ocular retention. To enhance its residence time and therapeutic efficacy, an ophthalmic nano-gel formulation was developed and optimized using statistical tools.
Methods: A nano-gel loaded with ganciclovir was formulated using a nanoparticulate drug delivery approach. Nanoparticles were prepared via the solvent evaporation method and incorporated into a thermosensitive in situ gel base. A 3² factorial design optimized key formulation parameters such as the concentration of ethyl cellulose and the concentration of polyvinyl alcohol, ensuring an ideal balance between particle size, % of encapsulation efficiency, and % of drug released at 12 hours. Further characterization studies for prepared ganciclovir nanoparticles were conducted including zeta potential and the polydispersity index. The final in situ gel was prepared by simple dispersion of the best-optimized batch of ganciclovir nanoparticles into 18 % w/v poloxamer solution, and this was evaluated by ex vivo permeation studies. Additionally, rheological assessments were performed to evaluate the gel’s residence time.
Results: The optimized formulation exhibited a nanosized drug carrier system with high drug entrapment efficiency and sustained drug release over 12 hours. Rheological studies confirmed its sol-to-gel transition at physiological ocular temperature, ensuring prolonged retention. Ex vivo permeation studies demonstrated enhanced drug permeation compared to conventional formulations. The Draize ocular irritation study in a rabbit model indicated that the final formulation is non-irritant.
Conclusion: The optimized ganciclovir-loaded ophthalmic nano-gel demonstrated improved ocular retention, controlled drug release, and enhanced permeation, making it a promising alternative for treating viral eye infections. The application of statistical optimization ensured formulation robustness, paving the way for further clinical investigations.
