Cationic Microemulsion of Voriconazole for the Treatment of Fungal Keratitis: In Vitro and In Vivo Evaluation

Abstract

Aim: This investigation aimed to develop a voriconazole-loaded chitosan-coated cationic microemulsion (CVME) to treat fungal keratitis. Methods: Microemulsions were prepared using water titration, and the optimized microemulsion was coated with chitosan to prepare CVME. The physicochemical parameters, ocular irritation potential, in vitro antifungal efficacy and in vitro release studies were performed. The in vivo antifungal efficacy study was conducted in a fungal infection-induced rabbit eye model. Results: The developed CVME displayed acceptable physicochemical properties and excellent mucoadhesive behavior and showed a sustained release profile. Ex vivo and in vivo studies concluded that higher permeability and improved antifungal efficacy were observed for CVME than drug suspension (DS). Conclusion: The prepared CVME7 is a viable alternative to treating fungal keratitis with existing approaches.

Plain language summary

Nanotechnology can help resolve problems that are currently associated with eye medications. Microemulsions (MEs) are mixtures containing tiny droplets of oil and water, which are made stable by ingredients called surfactants (meaning a type of soap) and co-surfactants. The ability for medications to be released slowly in MEs makes them suitable for eye medications because they reduce the number of times eye drops need to be used each day. This study wanted to create a medicine called voriconazole-loaded chitosan-coated cationic microemulsion (CVME) to treat a fungal infection in the eye called keratitis. We made MEs by gradually adding a combination of oil, surfactant, and water together. Then, we coated the best MEs with a substance called chitosan to make CVME. We tested its physical and chemical properties, whether it irritated the eyes, how well it could fight fungus, and how it released medicine. We tested CVME on rabbits with a fungal eye infection. CVME had good physical and chemical properties and stuck well to the mucus on the surface of the eyes. It released the medicine slowly. The system created in this study is very important for treating fungal infections because it helps the medicine stay on the eye surface longer and allows it to better reach the infected areas of the eye. CVME7 might be a better option for treating fungal keratitis instead of other methods that are currently used.

Keywords::

• anti-fungal
• cationic microemulsion
• chitosan-coated microemulsion
• cremophore EL
• fungal keratitis
• linoleic acid
• mucoadhesive
• ocular irritation
• propylene glycol
• voriconazole

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.future-science.com/doi/suppl/10.4155/tde-2023-0069

Author contributions

P Mohan: investigation, data curation, writing – original draft. J Rajeswari: writing – original draft. K Kesavan: conceptualization, visualization, supervision.

Acknowledgments

The authors were extremely thankful to the Department of University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India, for providing permission to determine the sample’s particle size specification. We were grateful to the Department of Anatomy, AIIMS, New Delhi, India, for preparing the TEM images of the samples. To accomplish the antifungal efficacy studies, the authors would like to deeply thank the Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur. The authors immensely expressed our sincere thanks to Intas Pharmaceuticals Ltd (Ahmedabad, India) for the gift sample of voriconazole.

Financial disclosure

The financial and technical support for the research work was granted by Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (C.G), Chhattisgarh, India, in the form of a fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The financial and technical support for the research work was granted by Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (C.G), Chhattisgarh, India, in the form of a fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.