Iontophoresis-Enhanced Transdermal Delivery of Curcumin Micelles: Mechanisms of Penetration and Wound Healing.

The transdermal delivery of poorly water-soluble drugs is limited by low aqueous solubility and the stratum corneum permeability barrier. In this study, curcumin was formulated into self-assembled micelles using Tween 20 and polyethylene glycol 400, which exhibited a particle size of 12.5 nm, a zeta potential of -12.5 mV, and a 170-fold increase in solubility. The curcumin micelles (CM) were combined with constant-current iontophoresis (0.45 mA/cm2), to investigate the synergistic enhancement effects and underlying mechanisms. The results showed a 44.2-fold increase in cumulative release over 60 min, with a linear flux-current density relationship (R2 = 0.99). CM exhibited electro-responsive release with an approximate 20-min lag. Under a fixed 2 h total stimulation, pulsed current (4 pulses) nearly doubled the 8-h cumulative release compared to continuous current. Furthermore, both current density and electrode configuration were shown to influence penetration depth and width. Iontophoresis enabled CM to penetrate rat skin to a depth of 270 μm and increased intradermal retention by 258%. In a rat second-degree burn model, the combination therapy significantly accelerated wound healing via promoting angiogenesis, downregulating inflammatory cytokines, and enhancing collagen deposition.