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

Abstract

A 32 factorial design was used to develop Natamycin cubosome nanoparticles with enhanced cornealpermeation, so as to effectively treat ocular fungal keratitis. Probe sonication technique was deployed to disperse thedry lipidic film to obtain colloidal dispersion. The colloidal dispersion was characterized for critical quality attributessuch as particle size, poly dispersibility index (PDI), zeta potential and entrapment efficiency. The optimized batchexhibited a particle size of 158.2 nm, zeta potential -40 mV, PDI 0.328 in addition, entrapment efficiency of 99.85%. Thein vitro drug release of natamycin from optimized cubosome demonstrated a cumulative %drug release of 84.29% atthe end of 8 hours. The optimized cubosomal dispersion exhibited enhanced in vitro antifungal activity againstCandida albicans and Aspergillus fumigatus as compared to a pure drug suspension. The optimized formulation wasfurther analyzed for polarized light microscopy (PLM), transmission electron microscopy (TEM) and small angle Xray scattering (SAXS) to state the morphology of formed cubosome nanoparticles and was noted to be Im3mbicontinous cubic mesophasic structure. X-ray diffraction (XRD) studies affirmed the complete encapsulation ofnatamycin into cubosome vesicles. Ex vivo corneal permeation studies of optimized formulation revealed enhancedcorneal permeation in comparison to a pure drug suspension. The ocular irritation studies performed on rabbitsindicated the cubosome to be non-irritant. Finally, the developed natamycin cubosome nanoparticles demonstratedsustained drug release and increased corneal penetration. Thus, these cubosome nanocarriers present a propitiousdelivery system for effective management of ocular fungal keratitis.