Effects of Blood Flow on the in Vivo Recovery of a Small Diffusible Molecule by Microdialysis in Human Skin

Clough, Geraldine F.; Boutsiouki, Paraskevi; Church, Martin K.; Michel, C. C.

doi:10.1124/jpet.102.035634

Cited by 58 publications

(49 citation statements)

References 27 publications

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“…If the combined pump system were used in the model skin system, the effects of the flow rate on the R sys values could be examined over a wide range; the results would be helpful in understanding the effects of blood flow rate on the systemic absorption of drugs after topical application. 5) In addition, drugs bound with serum proteins can diffuse into the extracellular space of the inflamed tissue, whereas the protein-binding FP in the model skin system was kept in area (b) because of the low MWCO of the laminated membranes. Such a property of the model skin system might be good for simplification of drug disposition in local tissues with inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…However, in vitro experimental systems using such membranes are not suitable for evaluating the drug concentration profiles in skin because of the lack of local blood flow and physiological response. [3][4][5] Various experimental designs, including in situ skin permeation experiments and in vitro isolated skin perfusion experiments, have been developed to study the disposition of drugs in skin after topical application. [6][7][8] Although such experimental systems provide new knowledge about factors in the uptake of drugs into the blood flow in the skin, large numbers of experimental animals are required and experience surgical operation stress.…”

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confidence: 99%

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The Use of an Artificial Skin Model to Study Transdermal Absorption of Drugs in Inflamed Skin

Oshima

Suzuki

Yajima

et al. 2012

Biological & Pharmaceutical Bulletin

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Studies on drug disposition in inflamed skin are important for safe and effective application of topical drugs. Here, the absorption of flurbiprofen (FP) through inflamed skin was examined in vivo and in a skin-mimicking artificial model system. The model skin system consisted of a silicone membrane acting as a model stratum corneum, laminated dialysis membranes acting as a model of viable skin, and 2 microdialysis probes-one used for determination of FP concentration and one acting as a model vessel. This model system could be used for quantitative evaluation of complicated permeation processes. In the in vivo experiments, FP absorption was suppressed in rats with inflamed skin induced by an intracutaneous injection of a mixed solution of λ-carrageenan, zymosan, and casein. Bovine serum albumin solution was placed between the dialysis membranes in the model skin system to mimic protein leaching in skin; the results suggested that the delayed absorption of FP in inflamed skin was due to binding to serum proteins leaching in the tissue. Such a combination of in vivo experiments and a model skin system is useful for understanding complex phenomena in inflamed and damaged skin and reduces experimental animal use.Key words skin absorption; model skin system; inflamed skin; protein binding; flurbiprofen Although permeation through the stratum corneum is the rate-limiting step for transdermal absorption of drugs, the kinetics of drug transfer in the viable epidermis and dermis could influence the pharmacological effects of a drug systemically as well as locally. Prolonged retention of the drug in the epidermis could delay onset of the therapeutic effect and/or cause undesirable side effects in the local tissue. Binding of drugs to tissue components in the skin could relate to retention of the drugs. In the case of inflamed skin, the leaching of plasma proteins with drug-binding ability could also affect the disposition of the drugs in local tissue. 1,2) In the drug of low protein binding ratio, the effect of plasma proteins leached into the local tissue will be small, the drug of high protein binding ratio are conversely susceptible to leach of plasma proteins. Although most skin formulations are intended for sound skin without injury or inflammation, prolonged or repeated application can bring about skin inflammation; also, some topical preparations are applied specifically to treat skin with inflammation. Therefore, studies on drug disposition in inflamed skin are important for safe and effective application of topical drugs.Excised animal skin is usually used for in vitro permeation studies in the early stages of the formulation development of new products. However, in vitro experimental systems using such membranes are not suitable for evaluating the drug concentration profiles in skin because of the lack of local blood flow and physiological response.3-5) Various experimental designs, including in situ skin permeation experiments and in vitro isolated skin perfusion experiments, have been developed to study the d...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Use of an Artificial Skin Model to Study Transdermal Absorption of Drugs in Inflamed Skin

Oshima

Suzuki

Yajima

et al. 2012

Biological & Pharmaceutical Bulletin

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“…where C tissue and C outlet are the concentration of the solute in the tissue and outfl ow of the probe, PS is the permeabilitysurface area product for the dialysis membrane, and F is the perfusion rate 31 is initially between 25 and 30 mg/mL but falls to 4 to 6 mg/mL after extended periods of perfusion.…”

Section: Principles Of Dialysis Of Large Moleculesmentioning

confidence: 99%

Microdialysis of large molecules

Clough

2005

AAPS J

113

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“…Skin irritation refers to a physiological reaction to a stimulus due to a local inflammatory response and such irritations can be visualized as erythema and edema (Clough et al, 2002). Rash, skin inflammation, swelling, scaling and abnormal tissue growth are commonly observed in the area affected by skin irritation reactions (Veronesi et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Dermal Toxicity of a Repellent Formulation Containing <i>Piper Aduncum</i> Linnaeus (Piperales: Piperaceae) Essential Oil

Mamood¹,

Othman²,

Nasir³

et al. 2017

American Journal of Pharmacology and Toxicology

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Abstract:It has been shown in previous research that Piper aduncum Linnaeus essential oil has the potential to be developed as an alternative mosquito repellent. When the essential oil was formulated into cream, it was able to provide >2h of protection against Aedes aegypti in the laboratory; thus, it can be commercialized as an alternative to synthetic repellent especially N, N-diethyl-3-methylbenzamide (DEET). In this study, the irritation and sensitization potential of a cream formulation containing P. aduncum essential oil was investigated to verify its safety for application purposes. The P. aduncum essential oil was formulated into a cream containing 10% of the essential oil for irritation and skin sensitization assays on New Zealand white rabbits and guinea pigs (Hartley strain), respectively, following the ISO10993-10:2010 (E) guidelines. The macroscopic and histological observations from both assays revealed that the cream formulation containing P. aduncum essential oil caused slight irritation on rabbit skin, with a Primary Irritation Index (PII) of 1.54; however, no positive response was detected in the skin sensitization assay. In conclusion, the cream formulation containing 10% P. aduncum essential oil was slightly irritating to rabbit skin but did not cause sensitization in the animals tested.

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Effects of Blood Flow on the in Vivo Recovery of a Small Diffusible Molecule by Microdialysis in Human Skin

Cited by 58 publications

References 27 publications

The Use of an Artificial Skin Model to Study Transdermal Absorption of Drugs in Inflamed Skin

The Use of an Artificial Skin Model to Study Transdermal Absorption of Drugs in Inflamed Skin

Microdialysis of large molecules

Dermal Toxicity of a Repellent Formulation Containing <i>Piper Aduncum</i> Linnaeus (Piperales: Piperaceae) Essential Oil

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