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Rabbit Skin (rabbit + skin)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

In vitro permeation of diclofenac sodium from novel microemulsion formulations through rabbit skin

DRUG DEVELOPMENT RESEARCH, Issue 1 2005
Gülten Kantarc
Abstract In order to increase topical penetration of the nonsteroidal anti-inflammatory drug, diclofenac sodium, new microemulsion formulations were prepared to increase drug solubility and in vitro penetration of the drug. The influence of dimethyl sulfoxide and propylene glycol were also investigated as enhancers on the in vitro penetration of diclofenac sodium using Franz diffusion cells using excised dorsal rabbit skin. Factorial randomized design was performed to analyze the results of in vitro permeation studies. Microemulsions prepared with isopropyl alcohol were superior to those prepared with propanol. Enhancers had different effects depending on the formulation. Propylene glycol was superior to dimethyl sulfoxide when incorporated into isopropyl alcohol microemulsion, whereas dimethyl sulfoxide was superior to propylene glycol in propanol microemulsions. There were no observable histopathological differences between the skin of the control group and the treated groups at the light microscope level due to swelling of the skin tissue. The present study shows that microemulsion formulations containing isopropyl alcohol as co-surfactant and propylene glycol as enhancer represent a promising approach for a topical vehicle for diclofenac sodium. Drug Dev. Res. 65:17,25, 2005. © 2005 Wiley-Liss, Inc. [source]

Percutaneous toxicokinetic and repeated cutaneous contact studies with ethylene glycol monohexyl ether

JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2003
Bryan 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]

The effects of heparin and related molecules on vascular permeability and neutrophil accumulation in rabbit skin

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2002
Helen Jones
Unfractionated heparin (UH) has been shown to possess a wide range of properties which are potentially anti-inflammatory. Many of these studies, including effects of heparin on adhesion of inflammatory cells to endothelium, have been carried out in vitro. In the present study, we have used radioisotopic techniques to study the effect of UH, and related molecules, on in vivo inflammatory responses (plasma exudation (PE) and PMN accumulation) in rabbit skin induced by cationic proteins, mediators and antigen. Intradermal (i.d.) pretreatment with UH dose-dependently inhibited poly-L-lysine (PLL)-induced responses. The same treatment had no effect on antigen (extract of Alternaria tenuis, AT)-, formyl-methionyl-leucyl-phenylalanine (fMLP)- or leukotriene (LT) B4 -induced responses, although i.d. dextran sulphate (DS) significantly inhibited responses to all of these mediators. High dose (10,000 u kg,1) intravenous UH significantly decreased cutaneous responses to fMLP and LTB4. By comparison, the selectin inhibitor, fucoidin, and DS, were very effective inhibitors of these responses, and of responses to AT and PLL. In contrast to the weak effect in the in vivo studies, UH significantly inhibited in vitro homotypic aggregation of rabbit PMNs, showing that it can modify PMN function. Our data with i.d. UH confirm the important ability of this molecule to interact with and neutralize polycationic peptides in vivo, suggesting that this is a prime role of endogenous heparin. The lack of effect of exogenous heparin on acute inflammatory responses induced by allergen, suggests that cationic proteins are unlikely to be primary mediators of the allergen-induced PE or PMN accumulation. British Journal of Pharmacology (2002) 135, 469,479; doi:10.1038/sj.bjp.0704505 [source]