Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis

A 32 factorial design was used to develop Natamycin cubosome nanoparticles with enhanced corneal permeation, so as to effectively treat ocular fungal keratitis. Probe sonication technique was deployed to disperse the dry lipidic film to obtain colloidal dispersion. The colloidal dispersion was characterized for critical quality attributes such as particle size, poly dispersibility index (PDI), zeta potential and entrapment efficiency. The optimized batch exhibited a particle size of 158.2 nm, zeta potential -40 mV, PDI 0.328 in addition, entrapment efficiency of 99.85%. The in vitro drug release of natamycin from optimized cubosome demonstrated a cumulative %drug release of 84.29% at the end of 8 hours. The optimized cubosomal dispersion exhibited enhanced in vitro antifungal activity against Candida albicans and Aspergillus fumigatus as compared to a pure drug suspension. The optimized formulation was further analyzed for polarized light microscopy (PLM), transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS) to state the morphology of formed cubosome nanoparticles and was noted to be Im3m bicontinous cubic mesophasic structure. X-ray diffraction (XRD) studies affirmed the complete encapsulation of natamycin into cubosome vesicles. Ex vivo corneal permeation studies of optimized formulation revealed enhanced corneal permeation in comparison to a pure drug suspension. The ocular irritation studies performed on rabbits indicated the cubosome to be non-irritant. Finally, the developed natamycin cubosome nanoparticles demonstrated sustained drug release and increased corneal penetration. Thus, these cubosome nanocarriers present a propitious delivery system for effective management of ocular fungal keratitis.