The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform
Jongwon Shim - One of the best experts on this subject based on the ideXlab platform.
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tocopheryl acetate nanoemulsions stabilized with lipid polymer hybrid emulsifiers for effective skin delivery
2012Co-Authors: Jaeyoon Park, Jongwon ShimAbstract:Abstract Tocopheryl acetate is used as the oil component of nanoemulsions using a mixture of unsaturated phospholipids and polyethylene oxide-block-poly(ɛ-caprolactone) (PEO-b-PCL). This study investigates the effects of the lipid–polymer composition on the size and surface charge of nanoemulsions, microviscosity of the interfacial layer, and skin absorption of tocopheryl acetate. The lipid–polymer hybrid system exhibits excellent colloidal dispersion stability, which is comparable to that of polymer-based nanoemulsions. If lipids are used as emulsifiers, nanoemulsions show poor dispersion stability despite a good skin absorption enhancing effect. The amount of tocopheryl acetate absorbed by the skin increases with an increased lipid-to-polymer ratio, as determined using the Hairless Guinea Pig skin loaded in a Franz-type diffusion cell. An 8:2 (w/w) mixture of unsaturated phospholipids and PEO-b-PCL exhibits the most efficient delivery of tocopheryl acetate into the skin. Our results show that tocopheryl acetate is absorbed almost twice as fast by the lipid–polymer hybrid system than the nanoemulsions stabilized with PEO-b-PCL. This study suggests that the lipid–polymer hybrid system can be used as an effective means of optimizing nanoemulsions in terms of dispersion stability and skin delivery capability.
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tocopheryl acetate nanoemulsions stabilized with lipid polymer hybrid emulsifiers for effective skin delivery
2012Co-Authors: Yoon Sung Nam, Jaeyoon Park, Jongwon Shim, Jin Woong Kim, Jong Suk Lee, Sang Hoon HanAbstract:Tocopheryl acetate is used as the oil component of nanoemulsions using a mixture of unsaturated phospholipids and polyethylene oxide-block-poly(e-caprolactone) (PEO-b-PCL). This study investigates the effects of the lipid-polymer composition on the size and surface charge of nanoemulsions, microviscosity of the interfacial layer, and skin absorption of tocopheryl acetate. The lipid-polymer hybrid system exhibits excellent colloidal dispersion stability, which is comparable to that of polymer-based nanoemulsions. If lipids are used as emulsifiers, nanoemulsions show poor dispersion stability despite a good skin absorption enhancing effect. The amount of tocopheryl acetate absorbed by the skin increases with an increased lipid-to-polymer ratio, as determined using the Hairless Guinea Pig skin loaded in a Franz-type diffusion cell. An 8:2 (w/w) mixture of unsaturated phospholipids and PEO-b-PCL exhibits the most efficient delivery of tocopheryl acetate into the skin. Our results show that tocopheryl acetate is absorbed almost twice as fast by the lipid-polymer hybrid system than the nanoemulsions stabilized with PEO-b-PCL. This study suggests that the lipid-polymer hybrid system can be used as an effective means of optimizing nanoemulsions in terms of dispersion stability and skin delivery capability.
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transdermal delivery of mixnoxidil with block copolymer nanoparticles
2004Co-Authors: Jongwon Shim, Hyung Seok Kang, Won Seok Park, Ih Seop ChangAbstract:Abstract We evaluated the effect of hydrodynamic size of self-assembled nanoparticles on skin penetration of minoxidil in vitro and in vivo. Self-assembled 40- and 130-nm nanoparticles, both containing minoxidil, were prepared by solvent evaporation of poly(e-caprolactone)-block-poly(ethyleneglycol) and were applied onto the skin of both hairy and Hairless Guinea Pigs in the Franz diffusion cell. In hairy Guinea Pig skin, the permeation of the minoxidil that incorporated in 40-nm nanoparticles was 1.5-fold higher in the epidermal layer and 1.7-fold higher in the receptor solution than that of 130-nm nanoparticles. Nanoparticle size dependence on the permeation behavior of minoxidil was not observed for Hairless Guinea Pig skin in either the epidermal layer or the receptor solution. Phospholipid liposomes and ethanol–water admixture, on the other hand, containing the same amount of minoxidil did not show differences in the amount of permeation irrespective of the existence of hair follicles. Confocal microscopy coupled with in vivo and in vitro skin permeation results demonstrated that nanoparticles containing solutes penetrated mainly via shunt routes like hair follicles, resulting in skin absorption of solutes.
Robert L Bronaugh - One of the best experts on this subject based on the ideXlab platform.
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Influence of Metabolism in Skin on Dosimetry after Topical Exposure
2013Co-Authors: Robert L Bronaugh, Steven W. Collier, Sara E. Macpherson, Margaret E K KraelingAbstract:Metabolism of chemicals occurs in skin and therefore should be taken into account when one determines topical exposure dose. Skin metabolism is difficult to measure in vivo because biological specimens may also contain metabolites from other tissues. Metabolism in skin during percutaneous absorption can be studied with viable skin in flow-through diffusion cells. Several compounds metabolized by microsomal enzymes in skin (benzo[alpyrene and 7-ethoxycoumarin) penetrated human and Hairless Guinea Pig skin predominantly unmetabolized. However, compounds containing a primary amino group (p-aminobenzoic acid, benzocaine, and azo color reduction products) were substrates for acetyltransferase activity in skin and were substantially metabolized during absorption. A physiologically based pharmacokinetic model has been developed with an input equation, allowing modeling after topical exposure. Plasma concentrations in the Hairless Guinea Pig were accurately predicted for the model compound, benzoic acid, from in vitro absorption, metabolism, and other pharmacokinetic parameters.- Environ Health Perspect 102(Suppl 1 1):71-74 (1994) Key words: skin absorption, metabolism, dosimetry, pharmacokinetic mode
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In vivo and in vitro skin absorption of lipophilic compounds, dibutyl phthalate, farnesol and geraniol in the Hairless Guinea Pig.
2009Co-Authors: Khanh Doan, Robert L Bronaugh, Jeffrey J. YourickAbstract:The relationship between in vitro and in vivo skin absorption of lipophilic cosmetic ingredients (dibutyl phthalate (DBP, Log Kow: 4.45), farnesol (Log Kow: 5.77) and geraniol (Log Kow: 3.56) from an oil-in-water emulsion was investigated in the Hairless Guinea Pig. In vivo absorption of DBP, farnesol and geraniol 24 h after dermal application was 62.0 ± 2.0, 39.8 ± 2.5, and 15.1 ± 1.8% of the applied dose (%AD), respectively. In vitro absorption was measured at 24 and 72 h by using flow-through diffusion cells (0.64 cm2) with a receptor fluid consisting of HHBSS + 4% BSA. In vitro studies of DBP, farnesol and geraniol absorption over 24 h found 27.1 ± 1.9, 43.5 ± 3.3 and 45.9 ± 3.2%AD in receptor fluid, respectively, and over 72 h found 59.9 ± 3.2, 77.5 ± 7.1 and 49.0 ± 6.3%AD, respectively. We found that the amount of DBP absorbed in vivo after 24 h closely agreed with the amount of DBP found in the receptor fluid in vitro after 72 h. In contrast, the amount of topically applied farnesol absorbed in vivo after 24 h was similar to the amount of farnesol found in receptor fluid in vitro after 24 h. A direct comparison between the in vivo absorption of geraniol and the in vitro absorption at 24 and 72 h was not meaningful due to the rapid evaporation of geraniol from the skin. Our in vitro results suggest that lipophilic chemicals initially form a reservoir in skin, and the material in the reservoir may ultimately diffuse out of the skin into the receptor fluid within 72 h. Our results also demonstrate the utility of in vivo studies for resolving questions about the fate of lipophilic chemicals remaining in skin after in vitro absorption studies.
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the effects of an alpha hydroxy acid glycolic acid on Hairless Guinea Pig skin permeability
1999Co-Authors: Harolyn L Hood, Margaret E K Kraeling, M G Robl, Robert L BronaughAbstract:Abstract The barrier integrity of Hairless Guinea Pig skin after treatment with an alpha hydroxy acid was assessed through in vivo topical application of an oil-in-water emulsion containing 5 or 10% glycolic acid at pH 3.0. The control was a commercial moisturizing lotion, pH 7.8. A dosing regimen for the glycolic acid formulations that was tolerated by the Hairless Guinea Pigs and significantly decreased stratum corneum turnover time was determined using the dansyl chloride staining technique. Once-daily dosing of Hairless Guinea Pig skin for 3 weeks with the glycolic acid formulations resulted in approximately a 36–39% decrease in stratum corneum turnover time compared with the control lotion. After this treatment, Hairless Guinea Pigs were sacrificed for the in vitro measurement of the percutaneous absorption of [14C]hydroquinone and [14C]musk xylol. No significant differences in the 24-hour absorption of either test compound were found for skin treated with the control lotion or the glycolic acid formulations. There were also no significant differences found in the absorption of [3H]water through skin from the different treatment groups. Although no increase in skin penetration occurred after treatment with the glycolic acid formulations, histology revealed approximately a twofold increase in epidermal thickness. Also the number of nucleated cell layers nearly doubled in skin treated with 5% and 10% glycolic acid compared with the control lotion and untreated skin. These studies demonstrate that substantial changes in the structure of Hairless Guinea Pig epidermis can occur without significant effect on skin permeability of two model compounds.
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metabolism of benzocaine during percutaneous absorption in the Hairless Guinea Pig acetylbenzocaine formation and activity
1996Co-Authors: Margaret E K Kraeling, Raymond J Lipicky, Robert L BronaughAbstract:The effect of dose and enzymatic inhibition on the percutaneous absorption and metabolism of benzocaine was studied in vitro in the Hairless Guinea Pig. At the dose level of 2 μg/cm2, benzo
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characterization of esterase and alcohol dehydrogenase activity in skin metabolism of retinyl palmitate to retinol vitamin a during percutaneous absorption
1994Co-Authors: J Boehnlein, Adel Sakr, J L Lichtin, Robert L BronaughAbstract:Retinyl palmitate, a widely used ingredient in cosmetic products, is promoted for its beneficial effects on the appearance of skin. Previous studies suggest that enzymes are available in skin to metabolize this ingredient during skin absorption. Esterase activity hydrolyzes retinyl palmitate to retinol (vitamin A), which is oxidized in many tissues to retinoic acid primarily by alcohol dehydrogenase. The activities of esterase and alcohol dehydrogenase were characterized in Hairless Guinea Pig skin by using flow-through diffusion cells and radiolabeled model compounds (methyl salicylate and benzyl alcohol) previously shown to be metabolized by these enzymes. Methyl salicylate was hydrolyzed by esterase to a greater extent in viable skin than in nonviable skin. Glycine conjugation of salicylic acid and benzoic acid occurred only in viable skin. The metabolism of methyl salicylate and benzyl alcohol occurred to a greater extent in male Guinea Pig skin than in female Guinea Pig skin. The percutaneous absorption of both radiolabeled compounds was similar in viable and nonviable skin. About 30 and 18% of topically applied retinyl palmitate were absorbed from an acetone vehicle by Hairless Guinea Pig skin and human skin, respectively. Less than 1% of the applied dose of this lipophilic compound diffused from skin into the receptor fluid. Retinol was the only detectable metabolite of retinyl palmitate in both Hairless Guinea Pig and human skin. In human skin, 44% of the absorbed retinyl palmitate was hydrolyzed to retinol. The use of retinyl palmitate in cosmetic formulations may result in significant delivery of retinol into the skin.
Jaeyoon Park - One of the best experts on this subject based on the ideXlab platform.
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tocopheryl acetate nanoemulsions stabilized with lipid polymer hybrid emulsifiers for effective skin delivery
2012Co-Authors: Jaeyoon Park, Jongwon ShimAbstract:Abstract Tocopheryl acetate is used as the oil component of nanoemulsions using a mixture of unsaturated phospholipids and polyethylene oxide-block-poly(ɛ-caprolactone) (PEO-b-PCL). This study investigates the effects of the lipid–polymer composition on the size and surface charge of nanoemulsions, microviscosity of the interfacial layer, and skin absorption of tocopheryl acetate. The lipid–polymer hybrid system exhibits excellent colloidal dispersion stability, which is comparable to that of polymer-based nanoemulsions. If lipids are used as emulsifiers, nanoemulsions show poor dispersion stability despite a good skin absorption enhancing effect. The amount of tocopheryl acetate absorbed by the skin increases with an increased lipid-to-polymer ratio, as determined using the Hairless Guinea Pig skin loaded in a Franz-type diffusion cell. An 8:2 (w/w) mixture of unsaturated phospholipids and PEO-b-PCL exhibits the most efficient delivery of tocopheryl acetate into the skin. Our results show that tocopheryl acetate is absorbed almost twice as fast by the lipid–polymer hybrid system than the nanoemulsions stabilized with PEO-b-PCL. This study suggests that the lipid–polymer hybrid system can be used as an effective means of optimizing nanoemulsions in terms of dispersion stability and skin delivery capability.
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tocopheryl acetate nanoemulsions stabilized with lipid polymer hybrid emulsifiers for effective skin delivery
2012Co-Authors: Yoon Sung Nam, Jaeyoon Park, Jongwon Shim, Jin Woong Kim, Jong Suk Lee, Sang Hoon HanAbstract:Tocopheryl acetate is used as the oil component of nanoemulsions using a mixture of unsaturated phospholipids and polyethylene oxide-block-poly(e-caprolactone) (PEO-b-PCL). This study investigates the effects of the lipid-polymer composition on the size and surface charge of nanoemulsions, microviscosity of the interfacial layer, and skin absorption of tocopheryl acetate. The lipid-polymer hybrid system exhibits excellent colloidal dispersion stability, which is comparable to that of polymer-based nanoemulsions. If lipids are used as emulsifiers, nanoemulsions show poor dispersion stability despite a good skin absorption enhancing effect. The amount of tocopheryl acetate absorbed by the skin increases with an increased lipid-to-polymer ratio, as determined using the Hairless Guinea Pig skin loaded in a Franz-type diffusion cell. An 8:2 (w/w) mixture of unsaturated phospholipids and PEO-b-PCL exhibits the most efficient delivery of tocopheryl acetate into the skin. Our results show that tocopheryl acetate is absorbed almost twice as fast by the lipid-polymer hybrid system than the nanoemulsions stabilized with PEO-b-PCL. This study suggests that the lipid-polymer hybrid system can be used as an effective means of optimizing nanoemulsions in terms of dispersion stability and skin delivery capability.
Sang Hoon Han - One of the best experts on this subject based on the ideXlab platform.
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tocopheryl acetate nanoemulsions stabilized with lipid polymer hybrid emulsifiers for effective skin delivery
2012Co-Authors: Yoon Sung Nam, Jaeyoon Park, Jongwon Shim, Jin Woong Kim, Jong Suk Lee, Sang Hoon HanAbstract:Tocopheryl acetate is used as the oil component of nanoemulsions using a mixture of unsaturated phospholipids and polyethylene oxide-block-poly(e-caprolactone) (PEO-b-PCL). This study investigates the effects of the lipid-polymer composition on the size and surface charge of nanoemulsions, microviscosity of the interfacial layer, and skin absorption of tocopheryl acetate. The lipid-polymer hybrid system exhibits excellent colloidal dispersion stability, which is comparable to that of polymer-based nanoemulsions. If lipids are used as emulsifiers, nanoemulsions show poor dispersion stability despite a good skin absorption enhancing effect. The amount of tocopheryl acetate absorbed by the skin increases with an increased lipid-to-polymer ratio, as determined using the Hairless Guinea Pig skin loaded in a Franz-type diffusion cell. An 8:2 (w/w) mixture of unsaturated phospholipids and PEO-b-PCL exhibits the most efficient delivery of tocopheryl acetate into the skin. Our results show that tocopheryl acetate is absorbed almost twice as fast by the lipid-polymer hybrid system than the nanoemulsions stabilized with PEO-b-PCL. This study suggests that the lipid-polymer hybrid system can be used as an effective means of optimizing nanoemulsions in terms of dispersion stability and skin delivery capability.
H P Benschop - One of the best experts on this subject based on the ideXlab platform.
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intravenous toxicokinetics of sulfur mustard and its dna adducts in the Hairless Guinea Pig and marmoset
2009Co-Authors: J P Langenberg, W E T Spruit, Willem C Kuijpers, R H Mars, H P M Van Helden, G P Van Der Schans, H P BenschopAbstract:ln order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard the toxicokinetics of this agent as well as its major DNA-adducts are being studied in male Hairless Guinea Pigs for the intravenous, respiratory and percutaneous routes. A highly sensitive method for bioanalysis of the intact agent in blood and tissues was developed, involving gas chromatography with automated thermodesorption injection and mass-spectrometric detection. Deuterated sulfur mustard is used as the internal standard. The absolute detection limit is 700 fg for sulfur mustard, which corresponds with a detection limit in blood of ca. 5 pg/ml. DNA-adducts are measured via the previously developed immuno-slot-blot method, using antibodies directed against the adduct of sulfur mustard to guanine. The intravenous 96-h LD50 of sulfur mustard in the Hairless Guinea Pig was determined and appeared to be 8.2 mg/kg. The intravenous toxicokinetics of this dose in the Hairless Guinea Pig are characterized by a very rapid distribution phase and a very slow elimination phase. A rapid adduct formation occurs in blood and lung, and subsequently in other organs. The adduct levels in lung were remarkably high. A considerable repair of the adducts is observed within 6 h. However, at 2 days after administration of sulfur mustard adducts are still detectable in most of the organs studied. The intravenous toxicokinetics of sulfur mustard were also studied in the marmoset at a dose corresponding with 1 LD50 in the Hairless Guinea Pig. The results obtained sofar will be discussed.
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toxicokinetics of the nerve agent vx in anesthetized and atropinized Hairless Guinea Pigs and marmosets after intravenous and percutaneous administration
2003Co-Authors: Marcel J Van Der Schans, J P Langenberg, Brenda J Lander, Herma J Van Der Wiel, H P BenschopAbstract:In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(±)P(±)-soman and (±)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (±)-VX. A validated method was developed to determine blood levels of (±)-VX by means of achiral gas chromatography at blood levels ≥10 pg/ml. The ratio of the two enantiomers of VX in blood could be measured at levels ≥1 ng/ml by using chiral HPLC in combination with off-line gas chromatographic analysis. In order to obtain basic information on the toxicokinetics of (±)-VX, i.e., under conditions of 100% bioavailability, the blood levels of this agent were measured in Hairless Guinea Pigs at iv doses corresponding with 1 and 2 LD50. The derived AUCs indicate a reasonable linearity of the toxicokinetics with dose. Also, the toxicokinetics in marmoset primates was studied at an absolute iv dose corresponding with 1 LD50 in the Hairless Guinea Pig which led to approximately the same levels of (±)-VX in blood as observed at 2 LD50 in the Hairless Guinea Pig. Finally, the toxicokinetics of (±)-VX were measured in Hairless Guinea Pigs via the most relevant porte d' entree for this agent, which is the percutaneous route at a dose corresponding with 1 LD50 (pc). Large variations were observed between individual animals in the rate of penetration of (±)-VX and in concomitant progression of AChE inhibition in blood of these animals. Blood levels of (±)-VX increased gradually over a 6-h period of time. After a 7-h penetration period, the total AUC corresponded with 2.5% bioavailability relative to iv administration. In contrast with the G-agents C(±)P(±)-soman and (±)-sarin, stereospecificity in the sequestration of the two enantiomers of (±)-VX is not a prominent phenomenon. It appears that (±)-VX is substantially more persistent in vivo than the two G-agents. This persistence may undermine the efficacy of pretreatment with carbamates of percutaneous intoxication in particular due to gradual replacement of carbamate on AChE by (±)-VX, whereas classical treatment of intoxication with oximes is hampered by the short persistence of oximes relative to the agent. © 2003 Elsevier Science (USA). All rights reserved.
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(This classification will not change) Title Ongerubriceerd
1998Co-Authors: Pml -a, J P Langenberg, H P Benschop, Managementuittreksel Ongerubriceerd, Abstract OngerubriceerdAbstract:Toxicokinetics of sulphur mustard and its DNA-adducts in the Hairless Guinea Pig-DNA-adducts as a measure for epithelial damage. Midterm repor
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toxicokinetics of sulfur mustard and its dna adducts in the Hairless Guinea Pig
1998Co-Authors: J P Langenberg, Willem C Kuijpers, H P M Van Helden, G P Van Der Schans, H E T Spruit, Roos H Marsgroenendijk, H C M Van Dijkknijnenburg, Henk C Trap, H P BenschopAbstract:In order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard (SM) the toxicokinetics of this agent as well as its major DNA-adduct were studied in male Hairless Guinea Pigs for the intravenous, respiratory and percutaneous routes. the study comprised measurement of the concentration-time course of SM in blood and measurement of the concentrations of intact SM and its adduct to guanine in various tissues at several time points after administration of, or exposure to SM. SM was analyzed in blood and tissues by gas chromatography with automated thermodesorption injection and mass-spectrometric detection. DNA-adducts were measured via an immuno-slot-blot method.In contrast with nerve agents of the phosphofluoridate type, SM partitions strongly to various organs, especially the lung, spleen, liver and bone marrow. the respiratory toxicity of SM appears to be local, rather than systemic. Surprisingly, the maximum concentration of SM in blood upon percutaneous exposu...
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toxicokinetics of sulfur mustard and its dna adducts in the Hairless Guinea Pig dna adducts as a measure for epithelial damage
1996Co-Authors: J P Langenberg, H P Benschop, G P Van Der SchansAbstract:Abstract : The toxicokinetics of sulfur mustard (SM) as well as of its major DNA-adduct were studied in male Hairless Guinea Pigs for the intravenous, respiratory and percutaneous routes. The study comprised measurement of the concentration-time course of SM in blood and measurement of the concentrations of intact SM and its DNA-adduct in various tissues at several time points after administration of, or exposure to SM. SM was analyzed in blood and tissues by gas chromatography with large volume injection and mass-spectrometric or pulsed-flame photometric dejection. DNA-adducts were measured via an immunoslotblot assay or immunofluorescence microscopy. The intravenous toxicokinetics of SM are characterized by a very rapid distribution phase and a very slow elimination phase. SM partitions strongly to various organs. The toxicokinetics are non-linear with dose. The respiratory toxicity of SM appears to be of a local, rather than a systemic nature, since concentrations of SM in blood could only be found during and after nose-only exposure to 3 LCt50 (2,400 mg.min./m). SM could also be measured in blood during and after percutaneous exposure to 1 LCt50 (10,000 mg.min./m, estimated). Pretreatment of Hairless Guinea Pigs with the potential scavengers N-acetyl cysteine or cysteine isopropyl ester did not significantly increase the LCt50-value for nose-only exposure to SM vapor. Topical skin protectants 1511 and 2701 protected very well against skin damage resulting from exposure to SM vapor or liquid.
