Topical skin targeting effect of penetration modifiers on hairless mouse skin, pig abdominal skin and pig ear skin

摘要

Objective: This study was to investigate the topical skin targeting effects and mechanism of combination penetration modifiers of 1,2-hexanediol (or 1,2-heptanediol) and 1,4-cyclohexanediol on transdermal absorption of metronidazole (MTZ) in different skin models. Methods: Six formulations were applied to pig abdominal skin and pig ear skin models, respectively, and the results were compared with the previous data on hairless mouse skin worked out by our laboratory. Four parameters (flux, T_lag, Q₂₄ and targeting ratio) were used to evaluate permeability and targeting effect in skin. Results: The combined penetration modifiers played a general role on decreasing permeability without reducing skin retention. The most significant skin permeability decrement to MTZ was pig abdominal skin (permeability decrement was ～20% for hairless mouse skin, 60% for pig abdominal skin and 40% for pig ear skin, respectively) while the strongest skin targeting effect appeared in hairless mouse skin (targeting ratios were 1.79 for hairless mouse skin, 1.24 for pig abdominal skin and 1.05 for pig ear skin, respectively) under the role of penetration modifiers. Conclusions: Thickness of stratum corneum (SC) was the major factor impact on skin targeting effect. Selection criteria of skin models also have been discussed in this study.