Enhancing effect of temperature on the transmucosal penetration kinetics of 17 beta-estradiol.
Human vaginal mucosa may be used as a model of buccal mucosa for in vitro permeability studies using various chemical compounds. Rectilinear temperature dependence of water flux across vaginal mucosa between 25 degrees C and 41 degrees C has been shown. The objective of this study was to examine the behaviour of the above barrier on fluxes of 17 beta-estradiol at various temperatures. Frozen vaginal mucosa specimens from a single patient were used (snap-frozen in liquid nitrogen and stored at -85 degrees C). The permeability to tritiated 17 beta-estradiol was determined using a continous flow-through perfusion system at temperatures of 20 degrees C, 25 degrees C, 30 degrees C, 37 degrees C and 41 degrees C. Histological examinations were performed before and after permeability experiments. Estimated steady state flux values were used at 20 degrees C, 25 degrees C and 30 degrees C. Estimated and true mean 17 beta-estradiol steady state flux rates (20-24 h) were found to be 415 +/- 27 standard error of the Mean (SEM), 848 +/- 60 SEM, 1355 +/- 77 SEM, 1436 +/- 37 SEM and 1482 +/- 35 SEM cpm.cm-2.min-1, at temperatures of 20 degrees C, 25 degrees C, 30 degrees C, 37 degrees C and 41 degrees C, respectively. A non-linear regression analysis and plot (R2 = 0.9941) displayed a curvilinear flux-temperature relationship. The results from this study showed that, notwithstanding cellular damage, the principal physical permeability barrier governing permeation kinetics was non-linearly temperature-dependent between the temperatures studied, providing further support for the concept that this barrier is lipoidal in nature.
van der Bijl
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Department of Pharmacology, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg, 7505, South Africa. pvdb@sun.ac.za
van Eyk
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van der Bijl
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Kriel
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D000328:Adult; D002462:Cell Membrane / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure; D003593:Cytoplasm / Q000648:ultrastructure; D015194:Diffusion Chambers, Culture; D004958:Estradiol / Q000493:pharmacokinetics*; D005260:Female; D005615:Freezing; D006801:Humans; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D017711:Nonlinear Dynamics; D010539:Permeability; D013696:Temperature; D014621:Vagina / Q000378:metabolism / Q000473:pathology
D004958:Estradiol