Efinaconazole-Loaded Liposomal Nanocarriers: A Box-Behnken Design Approach in Formulation Designing and Optimization for Onychomycosis

To design, optimize, and evaluate efinaconazole-loaded liposomal formulation with sustained drug release, enhanced trans-ungual drug penetration, and improved drug retention for treatment of onychomycosis. Conventional topical therapies for onychomycosis are limited by poor nail permeability and low drug retention. The optimized liposomal nanocarrier system enhances trans-ungual drug penetration with sustains release kinetics showing potential for effective drug delivery and patient compliance. Liposomes encapsulating efinaconazole were synthesized via the ethanol injection technique. A Box-Behnken design was employed for optimization using Design Expert® software. The independent variables included phospholipid (HSPC), cholesterol, and stirring speed, while dependent variables were particle size, PDI, zeta potential, entrapment efficiency, and cumulative drug release. The optimized liposomes underwent comprehensive characterization including in vitro drug release, TEM, DSC, release kinetics, ex vivo nail permeation, and physical stability. The optimized formulation prepared with HSPC:cholesterol (4.83:1 w/w ratio) exhibited particle size of 190 nm, PDI of 0.187, zeta potential of -28.20 mV, and entrapment efficiency of 47.80%. It showed sustained release profile with 75.41% cumulative drug release at 12 h following Korsmeyer-Peppas kinetic model. TEM analysis confirmed spherical, nanosized, unilamellar vesicles, and the DSC indicated successful drug encapsulation. The ex vivo drug permeation across human nail plate showed approximately 1.7-fold higher permeation of liposomal formulation compared to pure drug solution. The optimized liposomal formulation closely matched the software-predicted values and demonstrated enhanced trans-ungual drug penetration, sustained drug release, and satisfactory physical stability, indicating its promising prospects as transungual drug delivery system.