Visionary NanoBoost: Revolutionizing ocular treatment with positively charged Leciplex for enhanced Fenticonazole nitrate ocular delivery
Asmaa Ashraf Nemr, Michael M. Farag, Doaa Hegazy, Heba Attia, Eman Abdelhakeem
Abstract
This work outlines the formulation and characterization of Fenticonazoleloaded LeciPlex (FCN-LPX), adopting a simple blending technique for the eradication of oculomycosis. Fenticonazole nitrate (FCN) is a pleiotropic fungistatic and fungicidal agent with sparse aqueous solubility, hampering its transcorneal permeation. Three independent factors were probed using a 2 3 factorial design (2 blocks, 2 replicates), namely, X 1 : Cationic surfactant type, X 2 : Amount of cationic surfactant (mM), and X 3 : Amount of soybean phosphatidyl choline (mM). The optimized formulation exhibited remarkable entrapment efficiency (82.74 % ± 0.67 %), as verified by DSC and FT-IR analysis. TEM imaging revealed uniformly nanosized vesicles (189.95 ± 2.90 nm) with a robust positive zeta potential (41.35 ± 2.62 mV), which preserved its stability following gamma sterilization and storage. The optimum FCN-LPX demonstrated a bi-phasic release pattern (48.18 % ± 5.65 % at 4 H and 92.85 % ± 6.77 % at 24 H) and notable mucoadhesive properties, ensuring complete drug release. Safety assessments, including pH, surface tension, and refractive index measurements, along with histopathological evaluation, confirmed the formulation's safety profile. Furthermore, FCN-LPX achieved superior ex-vivo transcorneal permeation (3.3-fold) and deeper in-vivo corneal uptake (2.4-fold) compared to conventional FCN suspension. Microbiological analysis highlighted the enhanced antifungal activity of FCN-LPX, evidenced by a larger inhibition zone (11 %), significantly lower minimal inhibitory and fungicidal concentrations (8-fold), as well as improved fungal biofilm inhibition and prolonged antifungal effect. In conclusion, FCN-LPX is a propitious nanoformulation for the effective eradication of persistent oculomycosis.