Engineered Multilamellar Cationic Liposomes with High Loading Efficiency and Stability for Enhanced Transdermal Delivery

Cationic liposomes (CLs) have been regarded as the most promising drug carriers of various therapeutics, with excellent biodegradability, enhanced permeation through the skin layers, and high nucleic acid encapsulation efficiency. However, the main challenges in using CLs as drug carriers include stimulation, stability, and effective transdermal delivery. Herein, we developed multilamellar cationic liposomes (MCLs) using soy lecithin (SL), cholesterol (Cho), and the cationic surfactant N-α-lauroyl-l-arginine ethyl ester monohydrochloride (LAE) in a polyol solvent. The MCLs, with an approximate size of 300 nm and an onion-like structure and <i>zeta</i> potentials ranging from 40 to 60 mV, were formed through a synergistic strategy combining long-range electrostatic induction with short-range hydrophobic and hydrogen bonding. The molecular assembly mechanism was investigated using isothermal titration calorimetry (ITC), 2D-ROESY, and theoretical calculations. Chick chorioallantoic membrane assays revealed minimal bleeding (ESI < 12), indicating "nonirritant" classification. The MCLs encapsulated retinol exhibited an encapsulation rate of 80.29% compared with traditional liposomes (85.73%) and unilamellar cationic liposomes (85.20%). Furthermore, the permeation behavior of MCLs in porcine ear skin tissues showed significantly higher cumulative release. This stable, high-efficiency MCL platform provides new strategic solutions for advanced transdermal delivery systems.