Ocular Delivery of Itraconazole Loaded Leciplex to Treat Fungal Infection

Abstract

Purpose

Fungal ocular infection is challenging to treat and remains significant cause of blindness globally. The complex structure and physiology of the eye limits the drug targeting to it. Furthermore, post COVID-19 revealed a greater number of patients suffering from fungal eye infection. Hence, current study aimed to develop itraconazole loaded leciplex to enhance the corneal residence time for effective treatment of ocular fungal keratitis infection.

Methods

Itraconazole loaded leciplex were prepared by one-step fabrication process using soy phosphatidyl choline, didodecyl dimethyl ammonium bromide and Transcutol HP. Formulation was optimized via Box-Behnken design. Leciplex were evaluated for particle size, entrapment efficiency, zeta potential, transmission electron microscopy, anti-fungal activity, in vitro release and ex-vivo permeation study through goat cornea, ocular irritation by using hen’s egg test on chorioallantoic membrane (HET-CAM) study and ex-vivo corneal toxicity study.

Results

Itraconazole leciplex exhibited spherical morphology with particle size of 142.5 ± 2.2 nm, entrapment efficiency 99.8 ± 1.8% and zeta potential 62.5mV. In vitro release revealed sustained release pattern of itraconazole leciplex. Further, ex-vivo corneal drug retention study revealed 43.3% retention at the cornea. HET-CAM study and ex-vivo corneal toxicity study confirmed non-irritancy and non-toxicity of leciplex for ocular use. Further, antifungal activity of itraconazole leciplex against Candida albicans demonstrated significantly higher antifungal activity than marketed formulation.

Conclusion

Thus, itraconazole-loaded cationic leciplex delivered itraconazole effectively at corneal surface and adhered at anionic mucosal surface via electrostatic attraction to effectively treat corneal infection fungal keratitis at anatomically challenging regions of the eye.