Untitled

Abstract

Enhanced flux of neutral solutes during transdermal iontophoresis is attributed largely to electroosmotic volume flow. In this study, the iontophoretic fluxes of tritiated water (3H2O) and 14C-labeled mannitol through hairless mouse skin (HMS) were determined. The following questions were addressed: (i) What is the variability of water flux during iontophoresis? (ii) To what extent is the iontophoretic flux of a neutral solute correlated with water flux? (iii) Does the intrinsic permeability of the skin to neutral solutes change following iontophoresis? (iv) What is the effect of low pH on electroosmotic volume flow? and (v) Does the skin remain permselective after removal of the stratum corneum? Transport of both water and mannitol reached steady-state levels during 10 hr of constant-current iontophoresis (0.36 mA/cm2). Anodal fluxes exceeded cathodal values. Cathodal mannitol flux was retarded, relative to passive transport, by net volume flow in the opposite direction, such that transport of this molecule increased significantly after the termination of current passage. Anodal equivalent volume flows for water and mannitol, respectively, were 2.7 (+/- 1.3) and 1.23 (+/- 0.59) microL/hr cm2, indicating that only approximately 50% of the water flux participated in the electroosmosis of mannitol. The passive permeability of water and mannitol after 10 hr of iontophoresis was, respectively, 6 and 30 times greater than the pretreatment values. At pH 7, the cationic permselectivity of HMS was marginal [the Na+ transport number (tNa+) was determined to be 0.46] and less than that reported for human skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Synergistic Effect of lontophoresis and a Series of Fatty Acids on LHRH Permeability through Porcine Skin

“…Wang et al 39 demonstrated that the permeability of hydrocortisone through hairless mouse skin was increased postiontophoretically, suggesting a current-induced effect. Kim et al 58 made the same observation for water and mannitol. Inada et al 38 examined the effects of applied constant voltage on human epidermis in vitro and assessed the ability of the membrane to recover from the electrical perturbation.…”

“…The next 8 h represents the passive transport profiles of LHRH, 12 h postrecovery (see the Experimental following current pretreatment with phosphate-buffered saline for 4 h at current densities of 0.25 and 0.50 mA/ cm 2 . 58 The resulting normalized fluxes were ∼2.5-fold higher than passive diffusion. Pikal and Shah 59 demonstrated that the passive flux of glucose across the skin, after application of the current of 3.2 mA/cm 2 for 3 h, was 10 times greater than before current application.…”

Richard Guy and His Collaborators: ‘Crackling' the Skin Code

“…Initially targeted were peptides; representative work is that by Green et al [84,85,86,87] providing a first systematic insight into the effects of molecular weight, log partition coefficient and ionization on iontophoretic transport; Langkjaer et al [88] on insulin analogues, Delgado-Charro and Guy [89,90 ]on luteinizing hormone-releasing hormone analogues and Hirvonen and Guy [91 ]and Hirvonen et al [92] on peptides. Due to its high importance in glucose sampling, electro-osmosis was also being investigated by Kim et al [20], and later by Santi and Guy [93,94]. A twist of chance (although Richard asked me to repeat the experiment 3 times before believing the data!)…”

“…Figure 1 shows Guy's top co-authors and most cited articles [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. The Potts and Guy paper ‘Predicting skin permeability' [3] is, of course, the winner.…”

Determination of glucose by capillary electrophoresis/laser‐induced fluorescence in transdermally collected samples

“…It is known that any changes in blood glucose concentration are transmitted to the subcutaneous fluid within 5 min [l]. The potential of using iontophoresis as a noninvasive sampling procedure to monitor glucose in humans has been shown recently [2][3][4]. Passive diffusion, however, has been ruled out previously as a method for sampling glucose from the subcutaneous fluid [4].…”