Norfloxacin loaded nano-cubosomes for enhanced management of otitis externa: In vitro and in vivo evaluation.

The research's goal is to design and formulate nano-structured cubosomes loaded with norfloxacin (NFX)formanagement of otitis externa. In this study, glyceryl monooleate (GMO) as lipid phase, Cremophor EL as surfactant and either Pluronic F108 or Pluronic F127 as stabilizer were the used ingredients. The nano-cubosomal formulation "CUB 1" (its dispersed phase is composed of GMO (95%), Cremophor EL (2.5%) and Pluronic F108 (2.5%)) was the best achieved one. It had small particles size (216.75 ± 2.47 nm), good polydispersity index (0.339 ± 0.012) and acceptable zeta potential (-41.2 ± 2.262 mV). Images obtained after transmission electron microscopy examination ensured nearly cubic shape of formed nanoparticles with excellent dispersibility. Moreover, micrographs of rabbit ear skin specimens examined by confocal laser microscopy ensured good permeation capability of nano-structured cubosomes.In addition, in vivoskin deposition results revealed that higher amount of NFX was deposited in the rabbit ear skin throughout the study period (10 h) compared to drug suspension. Additionally, histopathological results proved that NFX loaded cubosomes can be safely applied topically on ear skin without any signs of inflammation nor skin irritation. Accordingly, these results anticipated the nano-structured cubosomal capabilities as a favorable nano-carrier for dermal NFX delivery to external ear skin for enhancing the management of otitis externa.