Enhancing effect of alpha-monoisostearyl glyceryl ether on the percutaneous penetration of indomethacin through excised rat skin.
(49/693)
The enhancing effect of alpha-monoisostearyl glyseryl ether (GE-IS) on the percutaneous penetration of indomethacin (IM) from test solutions in propylene glycol (PG) was investigated using the excised abdominal skin of rats in vitro. The percutaneous penetration of IM into diffusion cells was significantly increased in the presence of 0.2% or 1% (w/w) GE-IS compared with enhancer-free PG solution. Permeation parameters of IM, such as lag time and permeability coefficient, revealed that GE-IS significantly augmented the percutaneous penetration of IM from PG. These results strongly suggested that GE-IS functions as a penetration enhancer of IM through rat skin. To elucidate the mode of action of GE-IS as a penetration enhancer, the solubility of IM in the test solution and the percutaneous penetration of IM through damaged skin from which the stratum corneum had been stripped were investigated. The results suggested that GE-IS acts directly on the stratum corneum and alters the permeability of the skin. (+info)
Dermal absorption and distribution of (14)C carbaryl in Wistar rats.
(50/693)
The level of (14)C carbaryl was determined in blood (leukocytes, erythrocytes, all blood cells, plasma) and organs (brain, heart, lungs, liver, spleen, skin at the site of exposure) of male Wistar rats after dermal administration. The application liquid was (14)C carbaryl solution in 96% ethyl alcohol. This preparation, possessing an activity of 670 kBq/ml, containing 1.67 mg of carbaryl, was applied to the skin of the tail according to Massmann's method in own modification. The amount of the preparation per 1 cm(2) of the tail skin was 0.19 mg of carbaryl (74.4 kBq). The tails of experimental rats were exposed to (14)C carbaryl by soaking for 4 h daily: once, twice or three times. Beta radiation from (14)C was measured in homogenized organs (brain, heart, lungs, liver, skin) and in blood by computer controlled Wallac scintillation counter Model 1409, using Multi Calc software. The dermal absorption of carbaryl at the site of exposure and in the surrounding area of about 2 cm was observed already during 4 hour exposure. Carbaryl reached plasma within 4 h of a single dermal exposure and penetrated into leukocytes, erythrocytes, heart, liver, lung, kidney and brain. The largest amount of (14)C carbaryl, about 2% of absorbed dose, was detected in liver (+info)
Transdermal drug delivery by electroporation applied on the stratum corneum of rat using stamp-type electrode and frog-type electrode in vitro.
(51/693)
Transdermal enhancement effects of electroporation applied only on the stratum corneum by two electrode types, the stamp-type electrode and the frog-type electrode, were investigated in vitro using excised rat skin. Carboxyfluorescein (CF) was selected as a model compound. The excised skin was set in a Franz type diffusion cell and a square wave electric pulse was applied to the stratum corneum under various electric pulse conditions. We determined the permeability of CF to the receptor compartment under these conditions. Voltage, electric pulse length, and number of electric pulses, were varied from 10 to 1000 V, 50 micros to 15 ms and 5 to 30 pulses, respectively. Flux rate was enhanced as the electric pulse condition strengthened. However, the maximum value was attained in the flux rate, above which no increase was observed despite strengthening of the electric pulse. Although at low electric pulses, the enhancement effect of the frog-type electrode was superior to that of the stamp-type electrode, the maximum flux rates were the same. These results indicate that electroporation on the stratum corneum using the stamp-type electrode or frog-type electrode, is useful for transdermal drug delivery. (+info)
Promoting mechanism of menthol derivative, 1-O-ethyl-3-buthylcyclohexanol, on the percutaneous absorption of ketoprofen.
(52/693)
Menthol derivatives were synthesized and evaluated for their promoting activity on the percutaneous absorption of ketoprofen and skin irritation in vivo, choosing O-ethylmenthol (MET) as the mother compound. The compound having a C-3 positionned n-butyl group (1-O-ethyl-3-n-buthylcyclohexanol, OEBC) indicated the most promoting activity and caused relatively little skin irritation. In order to understand enhancement mechanism of OEBC an in vitro permeation study of ketoprofen was performed. The time course of the cumulative amounts of drug permeated through the rat skin exhibited a linear relation after an initial lag time. This was analyzed in membrane diffusion model and the diffusion and partition parameters of ketoprofen were estimated. Both parameters were remarkably enhanced when a hydrogel containing a small quantity of OEBC (0.5%) was applied. Furthermore, to clarify the site of action of OEBC, we also investigated in vitro permeation study of ketoprofen employing different skins of state, reversed skin and stratum corneum stripped skin. When OEBC was added to the hydrogels which were applied to the reversed and stripped skins, almost no changes of the flux were observed compared with the control (without OEBC). These results suggested that the site of action of OEBC was stratum corneum. Morphological changes of the stratum corneum surface were microscopically observed with 0-2% OEBC. The spaces between the stratum corneum cells treated with 0.5-2% OEBC became extended and the shape of each cell became clear. This may suggest that the site of action of OEBC was the intercellular of stratum corneum. Furthermore, an electron spin resonance study was performed to investigate the effect of OEBC on the intercellular lipid bilayer fluidity of the stratum corneum and the rotational correlation times were calculated. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were used as the spin label. In use of OEBC, the fluidity of TEMPO labeled the stratum corneum lipid increased as the addition of OEBC. The results suggested that OEBC promote the penetration of drugs by enhancing fluidity of the local lipid bilayers around TEMPO. (+info)
Effects of double-chained cationic surfactants n-dimethyldialkylammoniums on skin permeation of benzoic acid through excised guinea pig dorsal skin: comparison of their enhancement effects with hemolytic effects on erythrocytes.
(53/693)
We examined the effects of the double-chained cationic surfactants dimethyidialkylammoniums (CH3)2N+ (CnH(2n+1))2 on the permeation of benzoic acid through excised guinea pig dorsal skin. Among five dimethyldialkylammoniums tested (n=10-18), dimethyldidecylammonium (n=10) had dose-dependent enhancement effects at concentrations of more than 20 microM. Compared with the marked enhancement effects of dimethyldialkylammoniums with relatively shorter alkyl chains, those of long-chain dimethyldialkylammoniums (n=16, 18) were much less. We compared the enhancement effects of these cationic surfactants on skin permeation with their hemolytic effects on guinea pig erythrocytes. Their enhancement effects corresponded to their hemolytic activity. The findings suggest that dimethyldialkylammoniums with relatively shorter alkyl chains, which form either vesicles with looser molecular packing or micelles and appear to be present as surfactant monomers in higher ratios than those with longer alkyl chains, favor the interaction with skin. Their enhancement mechanism is possibly similar to that of single-chained cationic surfactants. (+info)
Safety of the insect repellent N,N-diethyl-M-toluamide (DEET) in pregnancy.
(54/693)
The safety of daily application of N, N-diethyl-m-toluamide (DEET) (1.7 g of DEET/day) in the second and third trimesters of pregnancy was assessed as part of a double-blind, randomized, therapeutic trial of insect repellents for the prevention of malaria in pregnancy (n = 897). No adverse neurologic, gastrointestinal, or dermatologic effects were observed for women who applied a median total dose of 214.2 g of DEET per pregnancy (range = 0-345.1 g). DEET crossed the placenta and was detected in 8% (95% confidence interval = 2.6-18.2) of cord blood samples from a randomly selected subgroup of DEET users (n = 50). No adverse effects on survival, growth, or development at birth, or at one year, were found. This is the first study to document the safety of DEET applied regularly in the second and third trimesters of pregnancy. The results suggest that the risk of DEET accumulating in the fetus is low and that DEET is safe to use in later pregnancy. (+info)
Acute nicotine poisoning associated with a traditional remedy for eczema.
(55/693)
We present a case of severe acute nicotine poisoning in an 8 year old boy with moderate eczema after topical application of a traditional remedy from a book published in Bangladesh. Symptoms consistent with nicotine poisoning developed within 30 minutes of application of the remedy. The child subsequently improved with supportive care and was discharged after five days with no neurological sequelae. Diagnosis of nicotine poisoning was not initially made due to difficulty in obtaining an accurate history via an interpreter from the parents who did not speak English. Samples taken 12 hours after application of the remedy showed a serum nicotine of 89 microgram/l, serum cotinine of 1430 microgram/l, urine nicotine of 1120 microgram/l, and a urine cotinine of 6960 microgram/l confirming acute nicotine poisoning. (+info)
Effect of cetrimide and ascorbic acid on in vitro human skin permeation of haloperidol.
(56/693)
Permeation of haloperidol through the human skin in vitro was studied with two enhancers, cetrimide and ascorbic acid, at various concentrations. Amber glass Franz-type diffusion cells were used for the permeation studies and haloperidol was made soluble in aqueous solution with the aid of lactic acid. Donor solutions were prepared by adding excess of haloperidol to 0.03% (v/v) lactic acid solution with or without enhancers at concentrations 0.1, 0.3 and 0.6% (w/v) and stirred for 36 h at 32 degrees C before filtering. Ascorbic acid gradually increased the solubility of the haloperidol from that of the control where as cetrimide did not show any effect. Cetrimide concentration dependent increase in the permeability coefficient of haloperidol was observed. Mechanism of enhancement by cetrimide was probed with the diffusion profile kinetics and Fourier transform infrared (FT-IR) spectroscopy. Cetrimide was found to increase the thermodynamic activity of the drug in the skin. IR spectra of the stratum corneum treated with cetrimide showed time-dependent decrease in the intensity of the spectrum and dose-dependent decrease of lipid band but no change in the protein conformation. Cetrimide appears to interact with both the dermal keratin and lipids and this interaction was found to be irreversible. Ascorbic acid although increased the flux of haloperidol to the same extent at all concentrations from that of the control, decreased the permeability coefficient and enhancer index in a concentration dependent manner and this is due to the increased solubility of the drug in the vehicle. Both the enhancers did not change the lag time from that of the control. (+info)