Visionary NanoBoost: Revolutionizing ocular treatment with positively charged Leciplex for enhanced Fenticonazole nitrate ocular delivery

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 2³ factorial design (2 blocks, 2 replicates), namely, X₁: Cationic surfactant type, X₂: Amount of cationic surfactant (mM), and X₃: 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.