Variation Assessment for in Vitro Permeabilities through Yucatan Micropig Skin

Abstract

Animal skins are frequently used as an alternative to human skin in percutaneous absorption studies, because human skin is not always available and the use of human tissues and organs creates ethical problems. In addition, a large variation has been found among human skin specimens as a result of differences in gender, age, race and anatomical donor site. [1][2][3][4][5][6][7][8][9][10] Numerous animal models, including primate, porcine, mouse, rat, guinea pig and snake, have been utilized for skin permeability studies. 1,3,4,[11][12][13] Animal skins with a small variation in skin permeability may be much better than human skin for determining or estimating the skin permeability of drugs and for developing transdermal formulations. 1,14,15) In our earlier study, 16) we investigated the in vitro permeation studies of the three model drugs, nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP), through human abdominal skin (human skin) and Sprague-Dawley rat dorsal skin (SD rat skin) were performed using Franz-type diffusion cells. The three model drugs were selected because of their different log K ow (logarithm of octanol/water partition coefficient at 37°C) (Table 1). NR, ISDN and FP were used as hydrophilic, lipophilic and highly lipophilic drugs, respectively. The permeation rates of the three model drugs were determined, and their variations were evaluated. The inter-individual variations in human skin permeability for each model drug were larger than the intra-individual variations in human skin permeability. Although the interindividual variations in SD rat skin permeability for each model drug were much lower than those in human skin permeability, and the permeation rates of those drugs through the SD rat skin were approximately twice that through human skin.16) The markedly smaller variation in the permeability through SD rat skin compared with that through human skin indicated that the in vitro permeation studies using SD rat skin would be particularly useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability. Recently, pig skin has been frequently used for skin permeation studies. 1,[17][18][19][20][21][22] It has been reported that the histological characteristics and permeability properties of pig skin closely resemble those of human skin. 6,7,[23][24][25][26][27][28] In addition, the Yucatan micropig (YMP) has been utilized for numerous research applications and has been suggested as an animal The purpose of this study was to evaluate the variations in the in vitro Yucatan micropig (YMP) skin permeabilities of drugs and to clarify whether YMP skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate and flurbiprofen, through YMP skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs were determined, and their variations were evaluated. The inter-individual variations in YMP skin permeab...

Distribution of Polyphenols and a Surfactant Component in Skin during Aerosol OT Microemulsion-Enhanced Intradermal Delivery

“…3, enhanced skin delivery by microemulsions, especially by Aerosol OT microemulsion, was also confirmed in YMP skin, which is hairless and has been suggested to be a good model to predict human skin permeability, 19) as well as showing physiological similarity to human skin.…”

“…We used two kinds of mammalian skin as model skin for human skin, which are different in structure and solute permeability. 13,18,19) Using the value of 120 µm 22) as the thickness of the epidermis, it was estimated from the results in Fig. 4 that 62.5% of curcumin present in guinea pig skin distributed in the dermis, whereas a higher 71.5% of a smaller molecule, resveratrol, distributed in the dermis.…”

“…They have been utilized for skin permeability studies and have been clarified to be good models to predict human skin permeability, although solute permeability in guinea pig skin is higher than in human skin, and that in YMP skin is lower. 13,18,19) Logarithm values of the partition coefficients between noctanol and PBS for curcumin and resveratrol were 3.68 and 2.97, respectively; therefore, these polyphenols are relatively hydrophobic. As shown in Fig.…”

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

“…Yucatan micropig (YMP) skin was selected as a permeation membrane as it has been frequently used for skin permeation studies. [10][11][12] Drug permeability and histological characteristics such as hair density in porcine skin closely resemble human skin.…”

“…Yucatan micropig (YMP) skin was selected as a permeation membrane as it has been frequently used for skin permeation studies. [10][11][12] Drug permeability and histological characteristics such as hair density in porcine skin closely resemble human skin.13-16) Furthermore, electrical skin resistance was determined to investigate the effects of EtOH pretreatment on skin permeabilities of small ions such as Na + and Cl − . The authors declare no conflict of interest.…”