• YAKHAK HOEJI
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• v.60 no.1
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• pp.36-45
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• 2016

This study was aimed to enhance the percutaneous absorption of tizanidine hydrochloride (TZ) across Strat-M$^{TM}$ artificial membrane and excised hairless mouse skin using various vehicles and chemical permeation enhancers. Solubility studies were performed using hydrophilic and lipophilic vehicles. To initially evaluate vehicle effects on skin permeation, Strat-M$^{TM}$ membrane was adopted using Franz-type diffusion cells loaded with 0.4 mg donor dose. Effects of fatty acids on the permeation of TZ from PG and PGMC were compared, and the effects of various hydrophilic vehicles in the presence of linoleic acid were studied using excised hairless mouse skin specimens. The mean solubility (mg/ml) of TZ in hydrophilic vehicles was higher: water > PG > DMSO > ethanol > PEG 200 > NMP > PEG 300 > PEG 400 > DGME, and solubilities in lipophilic vehicles such as PGMC, PGMC, IPM, Captex 200 and Captex 300 were much less than 1.0 mg/ml. Permeation rates through StratTM membrane from pure vehicles were in the rank order: PGMC ${\geq}$ LBF > DMSO ${\geq}$ NMP ${\geq}$ PGML ${\geq}$ PG ${\geq}$ PEG 200 ${\geq}$ DGME ${\geq}$ EtOH. However, permeation rates of TZ through hairless mouse skin from pure vehicles were very low, although PG showed the highest flux ($1.66{\pm}0.28{\mu}g/cm^2{\cdot}hr$). Therefore, PG was selected in further studies. Addition of enhancers (3 v/v%) into PG markedly increased the flux (${\mu}g/cm^2{\cdot}hr$): oleyl alcohol ($14.9{\pm}3.1$) ${\geq}$ oleic acid ($14.5{\pm}1.6$) ${\geq}$ linoleic acid ($13.7{\pm}1.3$) > capric acid ($4.4{\pm}0.6$) > caprylic acid ($2.1{\pm}0.4$). Among hydrophilic vehicles with linoleic acid, PG and DMSO revealed relatively higher permeation for TZ. Increase of donor dose in PG resulted in dose-dependent permeation fluxes. These results suggest that permeation properties of TZ from nonaqueous solutions are markedly different between Strat-$M^{TM}$ membrane and excised hairless mouse skin, and transdermal delivery of TZ would be feasible with a combination of PG and enhancers.

• Applied Microscopy
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• v.28 no.2
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• pp.127-137
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• 1998

This study was observed of the skin that changed after irradiation of the ultraviolet A. All the mouse were hairless which the weight are about 25g and the ages $6\sim8$ weeks old. The mouse were divided into six groups; control, irradiated for 6 hours, 3 days, 7 days, 14 days, 21 days and 28 days. Each group was irradiated with ultraviolet that is $320nm\sim366nm$ of wavelengths. After irradiated, the skin was observed with the electron microscope and the light microscope. The results are as follow: 1) Light microscopy With following irradiation, the epidermis was not changed to most groups but at the 28 days group was thickened and deposit the melanocyte. The elastic fibers within the epidermis were thickened and twisted with following irradiation. 2) Eelectron microscopy The elastic fibers were slightly clumped at 6 hours group, mildly increased and partly aggregated in the 3 days group, branched and tangled at 7 days group, irregulated and electron density at 14 days group, sightly thickened and twisted at 21 days group, and randomly arranged, shortened, twisted, and electron density at 28 days group.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.234.1-234.1
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• 2003

The effects of vehicles and penetration enhancers on the in vitro permeation of ketorolac tromethamine (KT) across excised hairless mouse skins were investigated. Among pure vehicles examined, propylene glycol monolaurate (PGML) showed the highest permeation flux, which was 94.3${\pm}$17.3 mg/cm$^2$/hr. Even though propylene glycol monocaprylate (PGMC) alone did not show high permeation rate, the skin permeability of DT was markedly increased by the addition of diethylene glycol monoethyl ether (DGME); the enhancement factors were 19.0 and 17.1 at 20 and 40% of DGME, respectively. (omitted)

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.172-172
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• 2003

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a prototype of many halogenated aromatic hydrocarbons, is a ubiquitous, persistent environmental contaminant and displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic and tumor promoter. In this study, we investigated the tumor promotion effect of TCDD on the two-stage skin chemical carcinogenesis using hairless mouse (SKH1). We induced papillomas after treatment with N-methyl -N'-nitro-N-nitorsoguanidine (MNNG) as a initiator and TCDD as a promoter for 30 weeks. We found that the incidence or multiplicity of papillomas and hyperplastic nodules was maximally induced at MNNG-TCDD group compare to control, MNNG, and TCDD alone. These results suggesting that TCDD can acts as a potent promoter in the hairless mouse skin. In addition, we used cDNA microarray to detect the differential gene expression in normal, tumor surrounding, and tumor regions induced in hairless mouse skin by MNNG plus TCDD protocol. We found that 49 and 42 genes out of 5,592 genes associated with protein synthesis, cell organization, lipid transport and oxidative stress in tumor and surrounding regions were up- or down- regulated two fold or more, respectively. We are currently investigating how these genes play a role in TCDD-mediated chemical carcinogenesis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.3
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• pp.695-699
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• 2009

UV irradiation causes skin-aging involving coarse wrinkles, thickening, dyspigmentation, and rough skin surface. This study was carried out to develop health & functional food by using Korean red ginsneg and Fagopyrum esculentum extract mixture (RGFE) for prevention of skin wrinkles. The RGFE-treated group showed the more effective collagenase inhibition rate than the red ginseng (RG)-treated group. To investigate photo protective effects of RGFE on UV-induced damaged skin, SKH hairless male mice were orally administerd RGFE and regional treatment and irradiated with UV for up to 8 weeks. In RGFE-treated group, better skin, and less wrinkle formation were observed compared with UV group. Epidermal thickness of hairless mouse was significantly decreased in RGFE, RG, and Fagopyrum esculentum (FE) groups compared with UV group. These results demonstrate RGFE have photo-protective effects on UV-damaged hairless mouse skin.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.375-381
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• 2005

A rapid and specific high-performance liquid chromatographic method was developed and validated for the simultaneous determination of prostaglandin $E_{1}\;(PGE_{1})$ and prostaglandin $E_{1}$ ethyl ester $(PGE_{1}-EE)$ in hairless mouse skin homogenate. The sample treatment procedure involved deproteination and precipitation by acetonitrile. $PGE_{1}$ and $PGE_{1}-EE$ in supernatant were separated in a reversed-phase C18 column without being interfered by other components present in hairless mouse skin homogenate. 9-Anthracenecarboxylic acid was used as an internal standard. The retention times of $PGE_{1}$, 9-anthracenecarboxylic acid and $PGE_{1}-EE$ were, 4.5, 9.5 and 18.0 min, respectively. The assay showed linearity from 1 to $40\;{\mu}g/ml$ for both $PGE_{1}$ and $PGE_{1}-EE$. Precision expressed as RSD ranged from 2.3 to 14.1 % for $PGE_{1}$ and 1.6 to 11.0% for $PGE_{1}-EE$. Accuracy ranged from 100.5 to 119.6 % for $PGE_{1}$ and from 98.0 to 103.7% for $PGE_{1}-EE$. This method was employed successfully to follow the time course of concentrations of $PGE_{1}$ and $PGE_{1}-EE$ in hairless mouse skin homogenate for stability study.

• Polymer(Korea)
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• v.33 no.3
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• pp.237-242
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• 2009

This study examined the transdermal delivery of alendronate across hairless mouse skin. The effects of iontophoresis, perforation with a microneedle, and a combination of a microneedle pretreatment and iontophoresis were evaluated in vitro test. Hydrogel patches were polymerized by UN polymerization to supply a hydrogel patch to the iontophoretic transdermal drug delivery system. The alendronate content in the iontophoretic delivery patch was $5.0\;mg/cm^3$. The amounts of alendronate that permeated across the hairless mouse skin when current densities of 0.25 and $0.50\;mA/cm^2$ were supplied to the iontophoretic alendronate patch were $0.80{\pm}0.03$ and $2.00{\pm}0.02{\mu}g$, respectively. After pretreatment with a microneedle, the amounts of alendronate that permeated across the hairless mouse skin increased to $70.65{\pm}0.37$ and $162.23{\pm}0.40{\mu}g$, respectively. The biocompatibility of the iontophoretic alendronate patch was examined according to the international standardization organization 10993.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.113-117
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• 2002

Cyto-toxic effect of silver sulfadiazine (Ag-SD) on keratinocytes and its implication on wound healing process were investigated in $2^{nd}$ degree bum hairless mouse model. As a dermal model, HaCat (immortalized keratinocytes) monolayer culture in DMEM with 10% FBS was used. Cyto-toxicity of Ag-SD was estimated by measuring the cell viability using neutral red assay after adding the drug. The $2^{nd}$ degree bum was prepared on hairless mouse back skin (1 cm diameter) and dressings with Ag-SD were applied for 96 hr. The process of re-epithelialization and the presence of inflammatory cells were investigated and histology with Hematoxylin-Eosin staining was performed. Ag-SD displayed highly cyto-toxic effect on cultured HaCat cells in a concentration dependent manner $(1-100\;{\mu}g/mL)$. Topical application of Ag-SD (2%) could control the infection: no inflammatory cells were observed in histology. However the cyto-toxic effect of Ag-SD on skin cells induced the impairment in epidermal regeneration.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.1
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• pp.20-26
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• 2008

This study investigated the antioxidative effect of mugwort (Artemisia vulgaris L.) extracts in hairless mouse skin from oxidative stress induced by UV-irradiation. After topical application on hairless mouse back with basic skin lotion group (control), ascorbic acid group (AA-0.5%, AA-1.0%, AA-2.0%, and AA-5.0%), and mugwort extract group (ME-0.5%, ME-1.0%, ME-2.0%, and ME-5.0%), the animals were irradiated to increasing doses of UVB (60 $mJ{\sim}100$ mJ) for 4 weeks. Hydrogen peroxide of hairless mouse skin homogenate significantly decreased in 2% (p<0.05) and 5% (p<0.05) of ME and AA groups. Hydroxyl radicals were decreased significantly in both of 2% and 5% ME groups as compared to AA groups (p<0.05). Oxidative stress levels deduced by oxidized protein contents were greatly decreased ($14.6{\sim}18.5%$) in all ME treatment groups, while only at 2% of AA treatment group. Lipid peroxide contents were greatly inhibited in all ME and AA treatment groups (p<0.01). Application of ME significantly increased catalase activity, over 25% in all mugwort and AA groups. Glutathione peroxidase activities were increased up to $20.5%{\sim}32.8%$ in 2.0% and 5% ME groups, whereas it increased in all AA groups. These results suggested that mugwort extract was more effective than that of ascorbic acid in protecting hairless mouse skin from photo-irradiation, and can be used as an potential anti-aging cosmetic ingredients.

• Journal of Photoscience
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• v.9 no.2
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• pp.146-149
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• 2002

Oxidative stress evoked hy Ultraviolet (UV) exposure has been suggested to be involved in UV-induced skin carcinogenesis. In this study, the role of oxidative stress in UV-carcinogenesis was evaluated by applying N-Acetylcysteine (NAC) in animal model of hairless-mouse. NAC is known to be a precursor of glutathione, which was converted to glutathione in cytoplasm, acting as an intracellular free radical scavenger. The glutathione levels in hairless mouse skin after one time application of NAC increased significantly. With and without the pre-treatment of NAC, hairless-mice were exposed to UVB three times a week, at total dose 274.4 kJ in 80 times, and the timing of tumor-development, incidence of skin tumor and the histopathology of tumors were observed. 8-hydroxy-2'-deoxyguanosine (8-0HdG), a typical form of oxidative damage in DNA has been also investigated in the course of experiment. The decrease of 8-0HdG formation of UVB- exposed skin compared to controls was observed in the early stage of experiment in the NAC-treated mice. In addition, initial tumor development delayed significantly in NAC-treated group. Finally the number of the tumor developed in the NAC-treated mice was fewer though not significant. These results suggest that antioxidants may have inhibitory effect in the initial step of UVB-induced carcinogenesis of hairless mice.