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Pig Skin (pig + skin)
Selected AbstractsEstablishment and Characterization of a Normal Melanocyte Cell Line Derived from Pig SkinPIGMENT CELL & MELANOMA RESEARCH, Issue 4 2003Sophia Julé Several minipig strains develop spontaneous malignant melanoma. As a first step toward the analysis of genes involved in the tumoral progression of melanoma in these animal models, we developed culture conditions for pig melanocytes whereby melanocytes from normal epidermis can be isolated directly onto mitotically inactivated keratinocytes in Eagle's minimal essential medium supplemented with fetal calf serum, tetradecanoyl phorbol acetate (TPA) and cholera toxin. We also derived an immortal line of pigmented melanocytes from the epidermis of a healthy Meishan pig. This cell line, designated PigMel, retains differentiation function in culture, dependence on TPA and cholera toxin and a diploid chromosome number. PigMel melanocytes exhibit morphological and molecular characteristics common to normal mammalian skin melanocytes. [source] Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopeciaDRUG DEVELOPMENT RESEARCH, Issue 3 2003Allen L Seligson Abstract Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3-amino-2-hydroxy-2-methyl- N -(4-nitro-3-trifluoromethyl)phenyl) propanamide (BP-34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 ,M decreased expression of the AR in LNCaP human cells by 95%, its serum half-life was 6 h; it decomposes hydrolytically to BP-34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270,300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD50 in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double-blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP-34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292,306, 2003. © 2003 Wiley-Liss, Inc. [source] Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin modelEXPERIMENTAL DERMATOLOGY, Issue 8 2010Tim Maisch Please cite this paper as: Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin model. Experimental Dermatology 2010; 19: e302,e305. Abstract:, An ex vivo porcine skin model was utilized to analyse the penetration of 5-aminolevulinic acid (5-ALA) contained in a nanoemulsion-based formulation BF-200 ALA (10% 5-ALA-hydrochloride) versus 16% aminolevulinate methyl ester-hydrochloride in a commercially cream (MAL cream) by fluorescence microscopy of their common metabolite protoporphyrin IX (PpIX) after 3, 5, 8 and 12 h. Fluorescence signals of PpIX in pig skin treated with BF-200 ALA were stronger than those for MAL cream. At 8 and 12 h, the PpIX fluorescence signals were 4.8- and 5.0-fold higher than those measured after MAL cream application. Fluorescence signals of PpIX after application of BF-200 ALA were detected in deeper tissue layers of the epidermis than after application of MAL cream (97.2 ± 5.7 ,m for BF-200 ALA vs 42.0 ± 4.2 ,m for MAL cream). These data implicate that BF-200 ALA in photodynamic therapy might lead to a superior therapeutically effect of intraepidermal (in situ) squamous cell carcinomas. [source] Nerve growth factor-evoked nociceptor sensitization in pig skin in vivoJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010Roman Rukwied Abstract Peripheral sensitization of skin nociceptors by nerve growth factor (NGF) was explored in pig skin in vivo. As an objective output measure, the area of axon-reflex-mediated erythema was assessed upon mechanical, thermal, chemical, and electrical stimuli delivered at 1, 3, and 7 days after i.d. injection of 1 ,g NGF into the pig's back skin (n = 8). Pretreatment with NGF provoked a sensitization to mechanical (600 mN), thermal (10 sec 49°C) and chemical (15 ,l, pH 3) stimuli that lasted for 7 days. No sensitization, however, was found in response to weak mechanical (100 mN), weak thermal (10 sec 45°C), or electrical stimuli. Irrespective of the skin pretreatment (NGF or PBS vehicle control), the area of electrically induced erythema decreased upon repetition (days 1,7) by 70% (P < 0.05). Sensitization of sensory endings by NGF upon mechanical, heat, and chemical stimuli suggests recruitment of sensory transducer molecules [e.g., TRPV1, acid-sensing ion channels (ASICs)]. In contrast, the gradual decrease in electrically induced erythema over 7 days might be attributable to axonal desensitization and possibly activity-dependent down-regulation of sodium channels. Thus, long-lasting sensitization processes of nociceptor endings or axonal sodium channel desensitization mechanisms can be explored in the pig as a translational experimental animal model. © 2010 Wiley-Liss, Inc. [source] Prediction of steady-state skin permeabilities of polar and nonpolar permeants across excised pig skin based on measurements of transient diffusion: Characterization of hydration effects on the skin porous pathwayJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2002Hua Tang Abstract The applicability of a two-parameter Fickian diffusion model for predicting the skin steady-state permeability based on measurements of the transient transport of permeants across the skin was tested. Using five model permeants possessing different physicochemical properties and pig skin as the model membrane, the skin permeabilities predicted by the two-parameter Fickian diffusion model were compared with the measured skin permeabilities. Results show that the transient skin permeation profiles of the hydrophobic permeants, estradiol, testosterone, and dolichol, across split-thickness pig skin can be modeled adequately by the two-parameter Fickian diffusion model (with constant parameter values), and therefore, that this model can be utilized to shorten the experimental time required to determine the skin permeabilities of these compounds. However, the skin permeabilities of the highly hydrophilic permeants, mannitol and sucrose, predicted by the two-parameter Fickian diffusion model (with constant parameter values) were significantly lower than the experimentally determined values, indicating that the dominant skin pathway of polar permeants within the excised pig skin undergoes significant structural changes during the in vitro diffusion cell studies. Although the skin permeability values determined experimentally using the traditional steady-state method normally correspond to a highly hydrated skin sample, the two-parameter Fickian diffusion model enables an estimation of the skin permeability of the skin membrane at its less-hydrated state (a condition more representative of in vivo and clinical situations). Using the two-parameter Fickian diffusion model and a recently developed skin porous-pathway theory, the effects of skin hydration on the skin porous pathway within the excised pig skin were characterized. Specifically, we found that hydration leads to induction of new pores/reduction of the tortuosity of existing pores within the excised pig skin during the 48 h diffusion cell studies conducted, while the skin average pore radii remain relatively constant (,26 Å) for up to 48 h. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1891,1907, 2002 [source] Tocopheryl acetate disposition in porcine and human skin when administered using lipid nanocarriersJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2010Mojgan Moddaresi Abstract Objectives Assessing the delivery of a drug into the skin when it has been formulated within a nanocarrier is a complex process that does not conform to the conventions of traditional semi-solid formulations. The aim of this study was to gain a fundamental understanding of drug disposition in both human and porcine skin when applied using a lipidic nanocarrier. Methods A model system was generated by loading tocopheryl acetate into a well-characterised solid lipid nanoparticle and formulating this system as a traditional aqueous hyaluronic acid gel. Franz diffusion cells fitted with a silicone or nylon membrane were used to assess drug and particle transport independently whilst human and pig skin were employed to determine skin delivery. Key findings The tocopheryl acetate, when loaded into the solid lipid nanoparticles, did not release from the particle. However, 1.65 ± 0.90% of an infinite dose of tocopheryl acetate penetrated into the stratum corneum of pig skin when delivered using a nanoparticle-containing gel. Conclusions These results suggest that hydration of the stratum corneum in pig skin could lead to the opening of hydrophilic pores big enough for 50 nm-sized particles to pass into the superficial layers of the skin, a phenomenon that was not repeated in human skin. [source] In-vitro transcutaneous delivery of tamoxifen and ,-linolenic acid from borage oil containing ethanol and 1,8-cineoleJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2004Suzanna Ho The objective of this study was to examine the effects of ethanol and 1,8-cineole on the transcutaneous delivery of tamoxifen and ,-linolenic acid (GLA) as a two-pronged anti-breast cancer therapy. Formulations containing tamoxifen and varying concentrations of borage oil (,25% GLA), 1,8-cineole and ethanol were prepared and the simultaneous permeation of tamoxifen and GLA determined across full-thickness pig skin using Franz-type diffusion cells over 48 h. Analysis of tamoxifen and GLA (as methyl ester) were by reverse-phase HPLC. The highest flux of tamoxifen of 488.2 ± 191 times 10,3 ,g cm,2 h,1 was observed with a formulation containing 20% 1,8-cineole and 20% ethanol. The same formulation also provided the greatest flux of GLA, 830.6 times 10,3 ,g cm,2 h,1. The findings from this work demonstrate the ability of 1,8-cineole and ethanol to enhance the in-vitro permeation of tamoxifen and GLA across the skin and support the plausibility of simultaneously delivering tamoxifen and GLA transcutaneously as a two-pronged anti-breast cancer system. [source] In vivo pharmacokinetics of ketoprofen after patch application in the Mexican hairless pigBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2009Masafumi Horie Abstract To evaluate the pharmacokinetics of topical drugs, in vitro permeation studies are performed using sacrificed pig skin or human tissues resected at surgery; however, these methods have their limitations in in vivo pharmacokinetics. This study examined the usefulness of Mexican hairless pigs for in vivo pharmacokinetic study, especially the drug concentration in the tissues. A ketoprofen patch was applied on the back of Mexican hairless pigs for 24,h, followed by sequential collection of blood specimens from 0 to 36,h (n=3). Also, the skin, subcutaneous fat, fascia and muscle from the center of the site of application were excised at 12,h after the application (n=4). Ketoprofen was first detected in the plasma at 8,h, the concentration increasing up to 24,h; the plasma concentration began to decrease after the removal of the ketoprofen patch. Ketoprofen concentrations in the tissues decreased with increasing depth of the tissues, but the values in the deep muscles, being the lowest among the tissues examined, were still higher than those in the plasma. While the data of drug concentration in human tissue are difficult to test, the Mexican hairless pig model appears to be attractive for in vivo pharmacokinetic studies of topically applied ketoprofen. Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||