N-Palmitoyl-Glycine-Histidine (Pal-GH) is a novel low molecular weight gelator. In our\nprevious report, ivermectin, a lipophilic drug, was effectively delivered to skin tissue after topical\napplication with Pal-GH as a spray gel formulation, and a much higher skin concentration was\nconfirmed than with the administration of a conventional oral formulation. The objective of this\nstudy was to increase the skin permeation of metronidazole (MTZ), a hydrophilic drug, after the\ntopical application of Pal-GH gel. An evaluation of the combined effect of chemical penetration\nenhancers (CPEs), such as isopropyl myristate (IPM), propylene glycol (PG), ethanol, diethylene glycol\nmonoethyl ether, and dimethyl sulfoxide (DMSO), on skin permeation was also conducted. We found\nthat a 5% Pal-GH gel containing 1% MTZ (F5MTZ) exhibited a 2.7-fold higher MTZ permeation\nthrough excised hairless rat skin than its solution. Furthermore, F5PG-MTZ and F5IPM-MTZ further\nincreased the skin permeation of MTZ when compared to F5MTZ. Interestingly, F5PG-MTZ enhanced\nthe skin penetration of MTZ, although no enhancement effect was observed for an MTZ solution\ncontaining PG. Thus, a Pal-GH formulation containing PG and IPM may enhance the skin permeation\nof MTZ.
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