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

Abstract

A 3 2 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 Xray 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.

Nanocubosomal based in situ gel loaded with natamycin for ocular fungal diseases: development, optimization, in-vitro , and in-vivo assessment

“…Overall, the non-irritancy of ocular formulations containing Carbopol polymer is well-established (Gilhotra et al, 2011 ). Similar results were observed with the previously reported NT-loaded glyceryl monooleate/Span 80 cubosome dispersion and NT-loaded niosome hydrogel (El-Nabarawi et al, 2019 ; Kazi et al, 2020 ).…”

“…Moreover, the release of NT from F3 was lower than that from the NT suspension. However, the in vitro of NT observed in the present study was higher than that from the previously reported NT-loaded glyceryl monooleate/Span 80 cubosome dispersion (Kazi et al, 2020 ). The reported study observed around 85% release only after 8 h, but with an initial burst release.…”

“…Nevertheless, the enhancement of NT permeation was less than that reported from transfersome-loaded gellan in situ gel wherein around 6- to 9-folds enhancement was noted (Janga et al, 2019 ). Similarly, the reported NT-loaded glyceryl monooleate/Span 80 cubosome dispersion also showed enhanced permeation than from a suspension formulation (Kazi et al, 2020 ). Meanwhile, the permeability coefficient and steady-state flux were found to be higher from NT-loaded solid lipid nanoparticles compared to pure NT (Khames et al, 2019 ).…”

“…Recently, NT-loaded cubosome (using glyceryl monooleate/Span 80) dispersion in poloxamer has been reported for ocular delivery of NT (Kazi et al, 2020 ). However, phytantriol offers considerably higher structural stability than glyceryl monooleate in the formation of cubosomes (Rizwan et al, 2011 ).…”