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Percutaneous Absorption (percutaneou + absorption)
Selected AbstractsA very promising new glucolipidic surfactant: LipowheatTMINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2005A. Djedour Synopsis LipowheatTM is an entirely biodegradable 100% natural active ingredient, extracted from non-transgenic wheat. Thanks to its very interesting properties, it can integrate the composition of most cosmetic and pharmaceutical products. The aim of this work was first to realize a large range of stable simple or multiple emulsions, in order to determine and evaluate the ability of a new glucolipidic surfactant LipowheatTM to form and stabilize emulsions. The rheological properties of these emulsions were tested during a 30-day storage period at three different storage conditions (cold, room temperature and at 40°C). In addition to dynamic and static rheological tests, droplet size distribution of the cream was also determined. Furthermore, a stable simple emulsion was selected to realize percutaneous absorption and evaluate the properties of LipowheatTM. Résumé Ce travail a pour objectif de mettre à jour et d'évaluer les propriètés émulsionnantes d'un nouveau tensioactif de nature glucolipidique, connu jusqu'alors pour ses propriétés actives en cosmétologie: le LipowheatTM. Cette étude comporte plusieurs parties distinctes: 1) Formulation d'émulsions simples L/H et/ou H/L et multiples H/L/H stabilisèes par du LipowheatTM, avec des huiles variant par leur origine (naturelle ou synthétique) ainsi que par leur polarité. 2) Caractérisation rhéologique, granulométrique, et conductimétrique de ces émulsions après les avoir soumises pendant 30 jours à des conditions de vieillissement accéléré (conservation à température ambiante, à +4°C et +40°C) et ce, afin d'en retenir les plus stables pour la suite de l'étude. 3) Enfin, dans une dernière phase, les propriètés de ces crèmes dans le domaine de la libération dermopharmaceutique seront évaluées lors d'études in vitro. [source] Percutaneous toxicokinetic and repeated cutaneous contact studies with ethylene glycol monohexyl etherJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2003Bryan Ballantyne Abstract Ethylene glycol monohexyl ether (EGHE; CAS no. 112-54-4) is a liquid industrial chemical with a potential for skin contact. The toxicokinetics of EGHE was investigated in Fischer 344 rats and New Zealand White rabbits by intravenous (i.v.) and 48-h occluded epicutaneous dosing. Given i.v. to male rats (2.5,25 mg kg,1) [14C]EGHE demonstrated ,rst-order kinetics. Carbon-14 was eliminated mainly in urine (68,74%) as metabolites, with no free EGHE. The plasma free EGHE concentration declined rapidly post-dosing and was not detectable by 8 h. Similar results were obtained for [14C]EGHE given i.v. to male rabbits in the dosage range 1,10 mg kg,1, except that the metabolism of EGHE was more rapid, with no free EGHE being detectable in plasma by 1 h post-dosing. After cutaneous dosing of male and female rats with 25 mg kg,1, there was rapid percutaneous absorption, with >95% of the radiochemical dose being recovered. Percutaneous bioavailability was >75%. Carbon-14 was excreted in urine (21,33%) to a lesser extent than by the i.v. route, and 14CO2 and volatiles accounted for 15,18%. Carbon-14 recovery was low from tissues and organs (0.39,0.46%), with no preferential accumulation. Extensive metabolism was indicated by the rapid decline in plasma free EGHE, with none being detectable by 48 h. Free EGHE was not present in urine, and urinary radioactivity was associated with up to seven metabolites. After cutaneous dosing of male and female rabbits (10 mg kg,1) ca. 75% of the dose was recovered, most 14C being in urine (58,60%). Urine radioactivity was associated with up to nine metabolite peaks, but no free EGHE. The toxicokinetic ,ndings indicate a signi,cant percutaneous absorption of EGHE across both rat and rabbit skin, which is rapidly and extensively metabolized, with renal excretion being the principal route of elimination of metabolites. A 9-day repeated skin contact study in the male and female New Zealand White rabbit, using a dosage range of 44,444 mg kg,1 day,1, did not show any evidence for percutaneous systemic toxicity. Copyright © 2003 John Wiley & Sons, Ltd. [source] Site-specific percutaneous absorption of methyl salicylate and VX in domestic swineJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2002E. J. Scott Duncan Abstract The site specificity of the percutaneous absorption of methyl salicylate (MeS) and the organophosphate nerve agent VX (O -ethyl S -(2-diisopropylaminoethyl) methylphosphonothioate) was examined in anaesthetized domestic swine that were fully instrumented for physiological endpoints. Four different anatomical sites (ear, perineum, inguinal crease and epigastrium) were exposed to the MeS and the serum levels were measured over a 6-h time period. The dose absorbed at the ear region was 11 ,g cm,2 with an initial flux of 0.063 ,g cm,2min,1, whereas at the epigastrium region the dose absorbed was 3 ,g cm,2 with an initial flux of 0.025 ,g cm,2min,1. For this reason further studies were carried out with VX on the ear and the epigastrium only. In animals treated with agent on the epigastrium, blood cholinesterase (ChE) activity began to drop 90 min after application and continued to decline at a constant rate for the remainder of the experiment to ca. 25% of awake control activity. At this time there were negligible signs of poisoning and the medical prognosis was judged to be good. In contrast, the ChE activity in animals receiving VX on the ear decreased to 25% of awake control values within 45 min and levelled out at 5,6% by 120 min. Clinical signs of VX poisoning paralleled the ChE inhibition, progressing in severity over the duration of the exposure. It was judged that these animals would not survive. The dramatic site dependence of agent absorption leading to vastly different toxicological endpoints demonstrated in this model system has important ramifications for chemical protective suit development, threat assessment, medical countermeasures and contamination control protocols. Copyright © 2002 Crown in the right of Canada. Published by John Wiley & Sons, Ltd. [source] Use of methyl salicylate as a simulant to predict the percutaneous absorption of sulfur mustardJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2001Jim E. Riviere Abstract Exposure to chemical vesicants such as sulfur mustard (HD) continues to be a threat to military forces requiring protectant strategies to exposure to be evaluated. Methyl salicylate (MS) has historically been the simulant of choice to assess HD exposure. The purpose of this study was to compare the percutaneous absorption and skin deposition of MS to HD in the isolated perfused porcine skin flap (IPPSF). The HD data were obtained from a previously published study in this model wherein 400 ,g cm,2 of ]14C[-MS or ]14C[-HD in ethanol were topically applied to 16 IPPSFs and experiments were terminated at 2, 4 or 8 h. Perfusate was collected at increasing time intervals throughout perfusion. Radioactivity was determined in perfusate and skin samples. Perfusate flux profiles were fitted to a bi-exponential model Y(t) = A(e, , e,) and the area under the curve (AUC), peak flux and time to peak flux were determined. Sulfur mustard had more pronounced and rapid initial flux parameters (P < 0.05). The AUCs determined from observed and model-predicted parameters were not statistically different, although the mean HD AUC was 40,50% greater than MS. The HD skin and fat levels were up to twice those seen with MS, but had lower stratum corneum and residual skin surface concentrations (P < 0.05). Compared with other chemicals studied in this model, HD and MS cutaneous disposition were very similar, supporting the use of MS as a dermal simulant for HD exposure. Copyright © 2001 John Wiley & Sons, Ltd. [source] Deep percutaneous penetration into muscles and jointsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2006Christine M. Lee Abstract The transdermal absorption of drugs and its subsequent deep tissue delivery is a complex process, with many factors influencing the penetration mechanisms. Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the treatment of joint and muscle diseases. However, the dangers associated with oral medications highlight the need for alternative methods of targeting and retaining drugs; one such means is through topical delivery. The drug's lipophilicity, permeability, and fraction unbound found in the viable skin are some physiochemical factors influencing the delivery mechanism after transdermal absorption. These and other variables play a role in determining whether the drug reaches the deep tissues via direct penetration or from systemic redistribution. Pharmacokinetic models have been developed to help elucidate the penetration routes and efficacy for various drugs. While there are still uncertainties regarding the deep tissue penetration kinetics, improvements to current research methodologies may bring about a greater understanding of percutaneous absorption into the deep muscle and joints. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1405,1413, 2006 [source] Bioconversion of naltrexone and its 3-O-alkyl-ester prodrugs in a human skin equivalentJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2005Dana C. Hammell Abstract The purpose of this study was to compare the percutaneous absorption and bioconversion of naltrexone (NTX), naltrexone-3-O-valerate (VAL), and naltrexone-3-O-(2,-ethylbutyrate) (ETBUT) in a human skin equivalent model (EpiDermÔ) and in fresh human skin in vitro. NTX diffusion and metabolism to 6-,-naltrexol (NTXol) were quantitated and compared in the EpiDermÔ and in excised fresh human skin. VAL and ETBUT diffusion and bioconversion studies were also completed in EpiDermÔ. Naltrexone bioconverted to levels of 3,±,2% NTXol in the EpiDermÔ and 1,±,0.5% in fresh human skin. VAL hydrolyzed rapidly in the EpiDermÔ and mainly (93,±,4%) NTX was found in the receiver compartment, similar to human skin. More intact ETBUT permeated the EpiDermÔ tissue compared to VAL, and only 15,±,11% NTX was found in the receiver. Significantly higher fluxes of NTX and the prodrugs were observed with the EpiDermÔ compared to human skin. A similar flux enhancement level was observed for VAL, compared to NTX base, in the EpiDermÔ and the human skin. Metabolically active human epidermal models like EpiDermÔ are useful as an alternative experimental system to human skin for prediction of topical/transdermal drug/prodrug bioconversion. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:828,836, 2005 [source] Polymers effect on estradiol partition coefficient between powdered human stratum corneum and waterJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2002Ronald C. Wester Abstract Macromolecules have gained interest as drug entities unto themselves and as transport facilitators to alter initial phases of percutaneous absorption. Two macromolecular polymers (MW 2081 and 2565) were designed to hold cosmetics and drugs to the skin surface by altering initial chemical and skin partitioning. The effect of these polymers on the partition coefficient (PC) of estradiol with powdered human stratum corneum (PHSC) and water was determined. There was no statistically significant effect on the PC when the concentration of estradiol was increased 100-fold (0.028,2.8 ,g/mL), when the incubation time was increased from 0 to 24 h, or when PHSC was delipidized. The addition of a liphophilic polymer had no effect on the PC; however, the hydrophilic polymer showed a significant polymer concentration-dependent increase (p,<,0.01) in log PC for estradiol concentrations. Thus, a macromolecular chemical has the potential to alter the partitioning of chemical into the outer layers of skin, the first step in percutaneous absorption. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2642,2645, 2002 [source] Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: in-vitro characterization, ex-vivo and in-vivo studiesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2007Vanna Sanna Solid lipid nanoparticles (SLN) designed for topical administration of econazole nitrate (ECN), were prepared by o/w high-shear homogenization method using different ratios of lipid and drug (5:1 and 10:1). SLN were characterized in terms of particle size, morphology, encapsulation efficiency and crystalline structure. After incorporation of SLN into hydrogels, rheological measurements were performed, and ex-vivo drug permeation tests were carried out using porcine stratum corneum (SC). In-vivo study of percutaneous absorption of ECN as a function of application time and composition of gels was carried out by tape-stripping technique. Penetration tests of the drug from a conventional gel were performed as comparison. High-shear homogenization method resulted in a good technique for preparation of ECN-loaded SLN. Particles had a mean diameter of about 150 nm and a regular shape and smooth surface. The encapsulation efficiency values were about 100%. Ex-vivo tests showed that SLN were able to control the drug release through the SC; the release rate depended upon the lipid content on the nanoparticles. In-vivo studies demonstrated that SLN promoted a rapid penetration of ECN through the SC after 1 h and improved the diffusion of the drug in the deeper skin layers after 3 h of application compared with the reference gel. [source] Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcuminJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2003Jia-You Fang Curcumin is a predominant compound derived from the rhizomes of Curcuma longa L., and shows antibacterial, anti-inflammatory and antineoplastic activity. The in-vitro and in-vivo skin absorption of curcumin was investigated after application of enhancers using Wistar rat as an animal model. The enhancers selected in this study included terpenes, flavonoids and cholestanol. The irritant profiles of these enhancers were also established by transepidermal water loss (TEWL) and histological observations. Cyclic monoterpenes generally showed stronger enhancement of curcumin permeation than the other enhancers. Modulation of concentration and pretreatment duration of enhancers possibly indicated that the enhancers have varied ability and mechanisms to enhance curcumin permeation. Terpineol produced the highest TEWL values among the enhancers tested, whereas ketocholestanol produced no, or only a negligible, increase in TEWL as compared with control. The results showed that skin disruption and inflammation did not necessarily correspond to the enhancing efficiency of the enhancers. [source] Transdermal Delivery of the Potent Analgesic Dihydroetorphine: Kinetic Analysis of Skin Permeation and Analgesic Effect in the Hairless RatJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2000SATOSHI OHMORI Dihydroetorphine is an extraordinarily strong opioid analgesic. To assess its effectiveness after topical application in hairless rats we have examined the kinetic analysis of skin permeation through excised skin and the in-vitro reservoir effect of skin, and have investigated the predictability of plasma concentration and analgesic effect following in-vivo transdermal application. Dihydroetorphine was moderately permeable from an aqueous suspension through excised hairless rat skin. Dihydroetorphine flux from drug-dispersed pressure-sensitive adhesive tape was threefold that from the applied aqueous suspension. The fluxes through the abdominal and the dorsal skin during tape application fitted the Fickian diffusion equation well after the tape was removed peeling off the outer layer of the stratum corneum. The relationship between the plasma concentration and the analgesic effect was examined for four different rates of infusion of dihydroetorphine. A non-linear pharmacokinetic disposition was observed. Following abdominal (0.28 cm2, 20,g) and dorsal (0.50 cm2, 35,g) applications of the dihydroetorphine tape, plasma concentration (0.2-0.8 ng mL,1) and analgesic effect were maintained at a suitable level, for more than 8h, until removal of the tape. These profiles were predictable using the combined equation for percutaneous absorption, disposition and the analgesic effect, but the analgesic effect was slightly lower than the predicted value. The results show that it was possible to control the plasma concentration and the analgesic effect of dihydroetorphine by topical application of the analgesic using pressure-sensitive adhesive tape in the hairless rat. It was possible to predict the result using mathematical modelling. [source] Nuclear microscopy: A tool for imaging elemental distribution and percutaneous absorption in vivoMICROSCOPY RESEARCH AND TECHNIQUE, Issue 4 2007Ana Veríssimo Abstract Nuclear microscopy is a technique based on a focused beam of accelerated particles that has the ability of imaging the morphology of the tissue in vivo and of producing the correspondent elemental maps, whether in major, minor, or trace concentrations. These characteristics constitute a strong advantage in studying the morphology of human skin, its elemental distributions and the permeation mechanisms of chemical compounds. In this study, nuclear microscopy techniques such as scanning transmission ion microscopy and particle induced X-ray emission were applied simultaneously, to cryopreserved human skin samples with the purpose of obtaining high-resolution images of cells and tissue morphology. In addition, quantitative elemental profiling and mapping of phosphorus, calcium, chlorine, and potassium in skin cross-sections were obtained. This procedure accurately distinguishes the epidermal strata and dermis by overlapping in real time the elemental information with density images obtained from the transmitted beam. A validation procedure for elemental distributions in human skin based on differential density of epidermal strata and dermis was established. As demonstrated, this procedure can be used in future studies as a tool for the in vivo examination of trans-epidermal and -dermal delivery of products. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. [source] Elucidation of the percutaneous absorption of chromium compounds by functional proteomicsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 22 2009Tai-Long Pan Abstract Chromium compounds are known to be associated with cytotoxicity and carcinogenicity when applied via a skin route. The aim of this study was to evaluate the skin permeability and toxicological profiles of four chromium species. Chromium permeation across the skin, as determined by an in vitro Franz cell, decreased in the order of sodium chromate>potassium chromate>potassium dichromate>chromium nitrate. The uptake of chromium species within the skin generally showed a contrary trend to the results of permeation, although differences among the various compounds were not large. Levels of in vivo skin deposition of the four compounds showed no statistically significant differences. Potassium chromate produced the greatest disruption of the skin structure as determined by HE staining, followed in order by sodium chromate, potassium dichromate, and chromium nitrate. This indicates that hexavalent chromium elicited greater toxicity to the skin compared to trivalent chromium. A similar result was observed for the viability of skin fibroblasts. To improve our understanding of the molecular mechanisms leading to functional changes in proteins, proteomic tools, including 2-DE and MS techniques combined with sequence database correlations, were applied to identify target proteins altered by pathologic states. Eight protein spots, corresponding to cutaneous enzymes involved in energy metabolism and chaperon proteins, which were identified and discussed in this study, were associated with skin cytotoxicity, immunity, and carcinogenesis. In addition, functional proteomics of skin tissues may provide a promising tool for developing therapeutic strategies and can serve as the basis for further research. [source] Topical PTH (1,34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trialBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003M.F. Holick Summary Background There continues to be a need to develop new pharmacological approaches for treating the common skin disease psoriasis. Human skin produces parathyroid hormone related peptide. This peptide is a potent inhibitor of epidermal cell growth. Objectives A programme was initiated to determine whether an agonist of this peptide's receptor, PTH (1,34), could be developed as a drug to treat psoriasis. Methods PTH (1,34) was formulated in Novasome A® cream. Fifteen adult patients with chronic plaque psoriasis who had failed to respond to at least one standard treatment were enrolled in a randomized double-blinded placebo self-controlled trial. The patients topically applied to a 25-cm2 psoriatic lesion 0·1 g of either Novasome A® cream or Novasome A® cream that contained 20 ,g of PTH (1,34) twice a day for 2 months. At the end of the double-blind study, patients were enrolled in an open large area study. Ten patients applied PTH (1,34) (50 ,g per 0·1 g) once daily to their psoriatic lesions. The patients were evaluated for their global improvement and calcium metabolism. Results Novasome A® cream enhanced the percutaneous absorption of PTH (1,34) in human skin in comparison with formulations in propylene glycol or normal saline. Psoriatic lesions treated with PTH (1,34) showed marked improvement in scaling, erythema and induration. There was a 67·3% improvement in the global severity score for the lesion treated with PTH (1,34) compared with the placebo-treated lesion, which only showed a 17·8% improvement. Ten patients topically applied PTH (1,34) on all of their lesions in a stepwise manner. A Psoriasis Area and Severity Index score analysis of all the patients revealed improvement of 42·6% (P < 0·02). None of the patients experienced hypercalcaemia or hypercalciuria or developed any side-effect to the medication. Conclusions Patients who were resistant to at least one standard therapy for psoriasis had a remarkable improvement in their psoriasis when they applied PTH (1,34) to their lesion(s). No untoward toxicity was observed in any of the subjects. This pilot study suggests that topical PTH (1,34) is a safe and effective novel therapy for psoriasis. [source] | |||||||||||||