Mucoadhesive Chitosan-Coated Cationic Microemulsion of Dexamethasone for Ocular Delivery: In Vitro and In Vivo Evaluation

ABSTRACT

Purpose: Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. However, its low aqueous solubility limits its clinical usefulness. The purpose of this study was to investigate the mucoadhesive chitosan-coated cationic microemulsions (CH-MEs) for ophthalmic delivery of DXN to treat uveitis.

Materials and methods: The pseudo-ternary phase diagrams were developed and various MEs were prepared using isopropyl myristate as oil, Tween 80 as a surfactant, propylene glycol as a co-surfactant and distilled water. MEs were prepared and coated with chitosan by the dropwise addition of chitosan solution in the ME dispersion. Physicochemical parameters (globule size, zetapotential, drug content, viscosity, refractive index and pH), mucoadhesive properties and the in vitro release of MEs were studied. The in vivo efficacy of prepared formulations and the marketed drug solution were studied by administering them topically to endotoxin-induced uveitis rabbit model.

Results: All formulations displayed an average globule size less than 200 nm and a positive surface charge. The developed CH-MEs showed acceptable physico-chemical behavior, good mucoadhesive properties, good stability for three months and exhibited sustained drug release. In vivo studies in rabbit eye showed a marked improvement in the anti-inflammatory activity of mucoadhesive CH-ME-treated eye compared with a marketed suspension formulation in a uveitis-induced rabbit eye model.

Conclusion: The developed CH-MEs are a viable alternative to conventional eye drops for its ability to enhance bioavailability through its longer precorneal residence time and its ability to sustain the release of the drug.

• cationic
• chitosan
• dexamethasone
• microemulsion
• mucoadhesive
• propylene glycol
• Tween 80
• uveitis

Acknowledgements

We acknowledge the help of Dr Gajendra Singh and Dr Madhu Yashpal, EM Facility, Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India, in carrying out the TEM analysis of samples and financial support from University Grants Commission, New Delhi, India, in terms of Senior Research Fellowship.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.