Curcumin-Loaded liposomes for topical ocular drug delivery: factorial screening, characterization, and ex vivo transcorneal permeation

Poor bioavailability from topical ophthalmic preparations arises chiefly from rapid precorneal drainage and the low permeability of the corneal epithelium, and for curcumin it is further limited by negligible aqueous solubility (<0.1 mg·mL−1). This study developed and characterized phospholipid liposomes loaded solely with curcumin as an anterior-segment ocular delivery system and evaluated their transcorneal permeation across excised rabbit cornea. Eight formulations were prepared by thin-film hydration according to a two-level full factorial design (2³) that varied curcumin concentration (0.5 and 1.0 mg·mL−1), lecithin content (4 and 5 mg) and probe-sonication time (5 and 10 min). Formulations were assessed for particle size, polydispersity index, zeta potential, encapsulation efficiency, pH, in vitro release and ex vivo transcorneal permeation using Franz diffusion cells (n = 3). Particle size ranged from 84 to 184 nm, zeta potential from −15.6 to −17.8 mV and encapsulation efficiency from 88.65% to 97.33%. Most formulations followed first-order release, whereas Lip-Cur-5 and Lip-Cur-6 followed Higuchi kinetics. Lip-Cur-5 (84 nm; 94.47% encapsulation) was identified as the lead formulation, achieving the highest steady-state flux (13.98 µg·cm−2·h − 1) and flux enhancement ratio (36.76). Factorial screening thus identified a lead curcumin liposome with markedly enhanced transcorneal permeation for topical anterior-segment delivery.