We investigated the skin permeation of 5-aminolevulinic acid (ALA) through Yucatan micropig full-thickness skin by using ALA-loaded W/O nanoemulsions composed of Span/Tween/ethanol (EtOH)/isopropyl palmitate (IPP)/10 wt% aqueous ALA solution. The nanoemulsions were prepared using Span 20/Tween 20 (S20/T20), Span 80/Tween 80 (S80/T80), and Span 20/Tween 80 (S20/T80) mixed surfactant systems. Based on the results of the phase diagram study and hydrodynamic diameter measurement of the nanoemulsions, we decided that the optimal weight ratio of Span/Tween/EtOH/IPP/10 wt% aqueous ALA solution in the nanoemulsion was 0.8/0.2/14/19/1.4. The permeability coefficient of ALA in the S20/T80 system was approximately five times larger than those in the S20/T20 and S80/T80 systems. The high skin permeation of ALA afforded by the ALA-loaded W/O nanoemulsion in the S20/T80 system is attributable to a significant enhancement in the partitioning of ALA to the stratum corneum.
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