Transdermal transport

Edwards, DA Danger, R, A Linear Theory of Transdermal Transport Phenomena, Journal of Pharmaceutical Sciences 83, 1315, 1994. 

Eq. 31 offered an easy method for predicting transdermal transport of small solutes (MW < 400 Da) but may not be used for larger molecules. The size of these larger molecules becomes comparable that of the lipid molecules and thus violates the underlying mechanistic model. 

Yu, B., Kim, K. H., So, P. T. C., Blankschtein, D., and Danger, R. 2002. Topographic heterogeneity in transdermal transport revealed by high-speed two-photon microscopy Determination of representative skin sample sizes. J. Inv. Dermatol. 118 1085-88. 

Willimann, H. and Luisi, P. L. (1991). Lecithin organogels as matrix for the transdermal transport of drugs. Biochem. Biophys. Res. Commun., 177, 897-900. 

Kararli T, Kirchhoff C, Penzotti S. Enhancement of transdermal transport of Azidothy-midine (AZT) with novel terpene and terpene-like enhancers—in vivo in-vitro correlations. J Control Release 1995 34 43-51. 

Dkeidek, I. 1999. Transdermal transport of macromolecules. MSc thesis, The Hebrew University of Jerusalem, Jerusalem, Israel. 

Transdermal iontophoresis involves the application of an electric field across the skin to facilitate (primarily) ionic transport across the membrane. Iontophoresis, it is important to point out, is differentiated from electroporation [14], another electrical approach to enhance transdermal transport, by the low fields employed. Whereas iontophoresis has achieved commercialization, there is (to our knowledge) no active development in progress of a transdermal delivery system employing electroporation. 

Peck, K.D., J. Hsu, S.K. Li, A.H. Ghanem, and W. Higuchi. 1998. Flux enhancement effects of ionic surfactants upon passive and electroosmotic transdermal transport. J Pharm Sci 87 1161. 

In contrast to low-current iontophoresis, which utilizes an electrical driving force to push permeants into and across the skin, electroporation increases transdermal transport primarily... 

Iontophoresis by definition is the process of transport of ions into or through a tissue by the use of an applied potential difference across the tissue [52], Depending on the physicochemical characteristics of a molecular species, electrorepulsion is usually the primary mechanism of transdermal transport for ions, whereas electroosmosis and increased passive diffusion (as a result of the reduced barrier properties) are more prominent for neutral species [53]. In contrast, enhancement in flux for neutral or weakly charged species during electroporation arises predominantly from the reduced barrier properties of the membrane, whereas direct electrorepulsion is usually of secondary importance [25],... 

Prausnitz, M.R., et al. 1996. Transdermal transport efficiency during skin electroporation and iontophoresis. J Control Release 38 205. 

Pliquett, U. 1999. Mechanistic studies of molecular transdermal transport due to skin electroporation. Adv Drug Deliv Rev 35 41. 

Vanbever, R., M.R. Prausnitz, and V. Preat. 1997. Macromolecules as novel transdermal transport enhancers for skin electroporation. Pharm Res 14 638. 

A recent work by Lavon et al. [74] suggests that the synergistic effect of SLS and ultrasound when applied simultaneously can also be attributed to the modification of the stratum corneum pH profile when exposed to ultrasound. The altered pH profile that results in improved SLS lipophylic solubility, together with improved SLS penetration and dispersion, can explain the synergistic enhancing effect on transdermal transport (see Figure 16.4). 

Ultrasound also exhibited a synergistic effect with electroporation [72], Ultrasound reduced the threshold voltage for electroporation as well as increased transdermal transport at a given electroporation voltage. The enhancement of transdermal transport induced by the combination of ultrasound and electroporation was higher than the sum of the enhancement induced by each enhancer alone. 

Boucaud, A., et al. 2001. In vitro study of low-frequency ultrasound-enhanced transdermal transport of fentanyl and caffeine across human and hairless rat skin. Int J Pharm 228 69. 

Merino, G., et al. 2003. Frequency and thermal effects on the enhancement of transdermal transport... 

Tezel, A., A. Sens, and S. Mitragotri 2003. A theoretical description of transdermal transport of hydrophilic solutes induced by low-frequency sonophoresis. J Pharm Sci 92 381. 

Kost, J., et al. 1996. Synergistic effect of electric field and ultrasound on transdermal transport. Pharm Res 13 633. 

Mitragotri, S., et al. 2000. Synergistic effect of low-frequency ultrasound and sodium lauryl sulfate on transdermal transport. J Pharm Sci 89 892. 

Lavon, I., N. Grossman, and J. Kost. 2005. The nature of ultrasound-SLS synergism during enhanced transdermal transport. J Control Release 107 484. 

Vanbever et al. [4] hypothesized that administration of macromolecules during electroporation would, in some fashion, stabilize aqueous pores produced by high-voltage pulsing. This group studied mannitol transdermal transport under electroporation with coadministered... 

Weaver, J.C., et al. 1997. Heparin alters transdermal transport associated with electroporation. Biochem Biophys Res Commun 234 (3) 637. 

Sen, A., et al. 2002. Enhanced transdermal transport by electroporation using anionic lipids. J Control Release 82 (2-3) 399. 

Smith, N., et al. 2003. Ultrasound-mediated transdermal transport of insulin in vitro through human skin using novel transducer designs. Ultrasound Med Biol 29 311. 

Kushner J, Kim D, So PTS, Blankschtein D, Langer RS. Dual-channel two-photon microscopy study of transdermal transport in skin treated with low-frequency ultrasound and a chemical enhancer. Journal of Investigative Dermatology 2007, 127, 2832-2846. 

I AM column chromatography has also been used to predict the transdermal transport of drugs [42], The retention time, log kw (capacity factor extrapolated to 100% aqueous phase at pH 5.5, IAM column) and log Poet. were compared for the studied drugs (Tables 4.11 and 4.12). The coefficients of permeability through human skin, Kp, were not correlated with either log fcw or log Poet.. The authors had, however, pre-... 

Transdermal transport of PG was followed vitro. Fullthickness skin, excised from hairless mice (StCH HR-1, Skin Cancer Hospital, Philadelphia, PA) and used immediately, was interposed between delivery system and receptor chamber. Serial samples of receptor fluid were collected and analyzed as before. Experiments were performed in quadruplicate. 

Dreher, F., Walde, R, Walther, P, and Wehrli, E. (1997), Interaction of a lecithin microemulsion gel with human stratum corneum and its effect on transdermal transport, J. Controlled Release, 45(2), 131-140. 

---