@article {NEMR2024105886,
	title = {Limonene-Enriched Ultra-Structural Cubosomes to Augment Ocular Delivery of a Poorly Water Soluble Anti-Fungal Drug: Fabrication, Characterization, Statistical Optimization, In vivo Corneal Uptake and Histopathological Evaluation in Rabbits},
	journal = {Journal of Drug Delivery Science and Technology},
	year = {2024},
	note = {n/a},
	pages = {105886},
	abstract = {<p>The target of this investigation was to obtain the composition of the optimized Fenticonazole nitrate(FCN)-loaded cubosomal formula that can prolong precorneal retention, increase corneal absorption, enhance corneal permeation, and anti-fungal efficacy of FCN. Cubosomes are bi-continuous structural vesicles fabricated using the hot emulsification technique in accordance with a 23-full factorial design. The selected fabrication factors were the concentration of the Lipid phase(X1), glyceryl monooleate: lipid phase stabilizer ratio(X2), and aqueous phase stabilizer types(X3). Whereas, the encapsulation efficiency percent(EE\%), Mean particle size(PS), Polydispersity index(PDI), and Zeta potential(ZP) were chosen as measured responses. The numerical optimization criterion of the design expert software was utilized to select the optimized formula(Op) for extra investigations. The Op formula had EE\% of 87.94{\textpm}0.7\%, PS of 249.75{\textpm}1.48nm, and ZP of -34.25{\textpm}0.64mV. The in vitro release study of the Op formula in comparison with FCN suspension showed a zero-order and controlled kinetic release behavior. Moreover, the results of the pH, refractive index, surface tension, and mucoadhesion study confirmed the superiority and the safety of the Op formula. Further, the ex vivo permeation study demonstrated a significant enhancement in the transcorneal permeation of the Op formula than FCN suspension by 2.69-fold. Besides, the in vivo corneal uptake confirmed the higher permeation of the Op formula in comparison with FCN suspension. Draize test and histopathological examination ensured the in vivo safety and tolerability of the Op formula. Overall, the previous findings ensured the efficacy of cubosomes in enhancing ocular retention, absorption, permeation, and bioavailability of FCN.</p>
},
	keywords = {cubosomes, Ex vivo corneal permeation, Fenticonazole nitrate, Fungal infection, Histopathological assessments, Ocular bioavailability},
	issn = {1773-2247},
	doi = {https://doi.org/10.1016/j.jddst.2024.105886},
	url = {https://www.sciencedirect.com/science/article/pii/S1773224724005550},
	author = {Asmaa Ashraf Nemr and Sadek Ahmed and Islam M. Adel}
}
