1 Brocks, DR, Mehvar, R. Rate and extent of drug accumulation after multiple dosing revisited. Clin Pharmacokinet 2010, 49:421–438.
2 Xu, L, Anchordoquy, T. Drug delivery trends in clinical trials and translational medicine: challenges and opportunities in the delivery of nucleic acid‐based therapeutics. J Pharm Sci 2011, 100:38–52.
3 Hamman, JH, Enslin, GM, Kotzé, AF. Oral delivery of peptide drugs: barriers and developments. BioDrugs 2005, 19:165–177.
4 Strack, T. The pharmacokinetics of alternative insulin delivery systems. Curr Opin Investig Drugs 2010, 11:394–401.
5 Foldvari, M, Baca‐Estrada, ME, He, Z, Hu, J, Attah‐Poku, S, King, M. Dermal and transdermal delivery of protein pharmaceuticals: lipid‐based delivery systems for interferon α
. Biotechnol Appl Biochem 1999, 30:129–137.
6 Yang, P, Singh, J, Wettig, S, Foldvari, M, Verrall, RE, Badea, I. Enhanced gene expression in epithelial cells transfected with amino acid‐substituted gemini nanoparticles. Eur J Pharm Biopharm 2010, 75: 311–320.
7 Barry, BW. Breaching the skin`s barrier to drugs. Nat Biotechnol 2004, 22:165–167.
8 Prausnitz, MR, Langer, R. Transdermal drug delivery. Nat Biotechnol 2008, 26:1261–1268.
9 Gray, GM, White, RJ, Williams, RH, Yardley, HJ. Lipid composition of the superficial stratum corneum cells of pig epidermis. Br J Dermatol 1982, 106:59–63.
10 Lampe, MA, Williams, ML, Elias, PM. Human epidermal lipids: characterization and modulations during differentiation. J Lipid Res 1983, 24:131–140.
11 Elias, PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 1983, 80:44s–49s.
12 Tojo, K. Random brick model for drug transport across stratum corneum. J Pharm Sci 1987, 76:889–891.
13 Abraham, W, Downing, DT. Lamellar structures formed by stratum corneum lipids in vitro: a deuterium nuclear magnetic resonance (NMR) study. Pharm Res 1992, 9:1415–1421.
14 El Maghraby, GM, Barry, BW, Williams, AC. Liposomes and skin: from drug delivery to model membranes. Eur J Pharm Sci 2008, 34:203–222.
15 Hansen, S, Naegel, A, Heisig, M, Wittum, G, Neumann, D, Kostka, KH, Meiers, P, Lehr, CM, Schaefer, UF. The role of corneocytes in skin transport revised‐a combined computational and experimental approach. Pharm Res 2009, 26:1379–1397.
16 Bouwstra, JA, Ponec, M. The skin barrier in healthy and diseased state. Biochim Biophys Acta 2006, 1758:2080–2095.
17 Foldvari, M, Badea, I, Wettig, S, Baboolal, D, Kumar, P, Creagh, AL, Haynes, CA. Topical delivery of interferon α
by biphasic vesicles: evidence for a novel nanopathway across the stratum corneum. Mol Pharm 2010, 7:751–762.
18 Landmann, L. Epidermal permeability barrier: transformation of lamellar granule‐disks into intercellular sheets by a membrane‐fusion process, a freeze‐fracture study. J Invest Dermatol 1986, 87:202–209.
19 Swartzendruber, DC, Wertz, PW, Kitko, DJ, Madison, KC, Downing, DT. Molecular models of the intercellular lipid lamellae in mammalian stratum corneum. J Invest Dermatol 1989, 92:251–257.
20 Robson, KJ, Stewart, ME, Michelsen, S, Lazo, ND, Downing, DT. 6‐Hydroxy‐4‐sphingenine in human epidermal ceramides. J Lipid Res 1994, 35:2060–2068.
21 Bouwstra, JA, Honeywell‐Nguyen, PL, Gooris, GS, Ponec, M. Structure of the skin barrier and its modulation by vesicular formulations. Prog Lipid Res 2003, 42:1–36.
22 Norlén, L. Skin barrier structure and function: the single gel phase model. J Invest Dermatol 2001, 117: 830–836.
23 Norlén, L. Skin barrier formation: the membrane folding model. J Invest Dermatol 2001, 117:823–829.
24 Wertz, PW. Lipids and barrier function of the skin. Acta Derm Venereol 2000, 208:7–11.
25 Bouwstra, JA, Gooris, GS, Weerheim, A, Kempenaar, J, Ponec, M. Characterization of stratum corneum structure in reconstructed epidermis by X‐ray diffraction. J Lipid Res 1995, 36:496–504.
26 Jungersted, JM, Høgh, JK, Hellgren, LI, Jemec, GBE, Agner, T. Ethnicity and stratum corneum ceramides. Br J Dermatol 2010, 163:1169–1173.
27 Groen, D, Gooris, GS, Bouwstra, JA. New insights into the stratum corneum lipid organization by X‐ray diffraction analysis. Biophys J 2009, 97:2242–2249.
28 Merle, C, Baillet‐Guffroy, A. Physical and chemical perturbations of the supramolecular organization of the stratum corneum lipids: in vitro to ex vivo study. Biochim Biophys Acta 2009, 1788:1092–1098.
29 Mendelsohn, R, Flach, CR, Moore, DJ. Determination of molecular conformation and permeation in skin via IR spectroscopy, microscopy, and imaging. Biochim Biophys Acta 2006, 1758:923–933.
30 Norlen, L, Plasencia, I, Bagatolli, L. Stratum corneum lipid organization as observed by atomic force, confocal and two‐photon excitation fluorescence microscopy. Int J Cosmet Sci 2008, 30:411.
31 Bouwstra, JA, Gooris, GS, van der Spek, JA, Bras, W. Structural investigations of human stratum corneum by small‐angle X‐ray scattering. J Invest Dermatol 1991, 97:1005–1012.
32 Bouwstra, JA, Dubbelaar, FE, Gooris, GS, Weerheim, AM, Ponec, M. The role of ceramide composition in the lipid organisation of the skin barrier. Biochim Biophys Acta 1999, 1419:127–136.
33 Forslind, B, Engström, S, Engblom, J, Norlén, L. A novel approach to the understanding of human skin barrier function. J Dermatol Sci 1997, 14:115–125.
34 Sznitowska, M, Janicki, S, Williams, AC. Intracellular or intercellular localization of the polar pathway of penetration across stratum corneum. J Pharm Sci 1998, 87:1109–1114.
35 Weaver, JC, Vaughan, TE, Chizmadzhev, Y. Theory of electrical creation of aqueous pathways across skin transport barriers. Adv Drug Deliv Rev 1999, 35: 21–39.
36 Sugar, IP, Neumann, E. Stochastic model for electric field‐induced membrane pores. Electroporation. Biophys Chem 1984, 19:211–225.
37 Turner, NG, Kalia, YN, Guy, RH. The effect of current on skin barrier function in vivo: recovery kinetics post‐iontophoresis. Pharm Res 1997, 14:1252–1257.
38 Greenbaum, SS, Bernstein, EF. Comparison of iontophoresis of lidocaine with a eutectic mixture of lidocaine and prilocaine (EMLA) for topically administered local anesthesia. J Dermatol Surg Oncol 1994, 20:579–583.
39 Henry, S, McAllister, DV, Allen, MG, Prausnitz, MR. Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci 1998, 87:922–925.
40 Fang, JY, Lee, WR, Shen, SC, Fang, YP, Hu, CH. Enhancement of topical 5‐aminolaevulinic acid delivery by erbium:YAG laser and microdermabrasion: a comparison with iontophoresis and electroporation. Br J Dermatol 2004, 151:132–140.
41 Burkoth, TL, Bellhouse, BJ, Hewson, G, Longridge, DJ, Muddle, AG, Sarphie, DF. Transdermal and transmucosal powdered drug delivery. Crit Rev Ther Drug Carrier Syst 1999, 16:331–384.
42 Lee, S, Kollias, N, McAuliffe, DJ, Flotte, T, Doukas, A. Topical delivery in humans with a single photomechanical wave. Pharm Res 1999, 16:1717–1721.
43 Barry, BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci 2001, 14:101–114.
44 Williams, AC, Barry, BW. Skin absorption enhancers. Crit Rev Ther Drug Carrier Syst 1992, 9:305–353.
45 Chattaraj, S, Walker, R. %22Penetration enhancer classification%22. In: Smith, EW, Maibach, HI, eds. Percutaneous Penetration Enhancers. Boca Raton, FL: CRC Press
; 1995, 5–20.
46 Hadgraft, J, Pugh, WJ. The selection and design of topical and transdermal agents: a review. J Investig Dermatol Symp Proc 1998, 3:131–135.
47 Cocera, M, Lopez, O, Coderch, L, Parra, JL, de la Maza, A. Influence of the level of ceramides on the permeability of stratum corneum lipid liposomes caused by a C12‐betaine/sodium dodecyl sulfate mixture. Int J Pharm 1999, 183:165–173.
48 Shokri, J, Nokhodchi, A, Dashbolaghi, A, Hassan‐Zadeh, D, Ghafourian, T, Barzegar Jalali, M. The effect of surfactants on the skin penetration of diazepam Int J Pharm 2001, 228:99–107.
49 Honeywell‐Nguyen, PL, Bouwstra, JA. The in vitro transport of pergolide from surfactant‐based elastic vesicles through human skin: a suggested mechanism of action. J Control Release 2003, 86:145–156.
50 Hadgraft, J, Walters, KA, Guy, RH. Epidermal lipids and topical drug delivery. Semin Dermatol 1992, 11: 139–144.
51 Hadgraft, J. Recent developments in topical and transdermal delivery. Eur J Drug Metab Pharmacokinet 1996, 21:165–173.
52 Marjukka Suhonen, T, Bouwstra, JA, Urtti, A. Chemical enhancement of percutaneous absorption in relation to stratum corneum structural alterations. J Control Release 1999, 59:149–161.
53 Mezei, M, Gulasekharam, V. Liposomes—a selective drug delivery system for the topical route of administration. I. Lotion dosage form. Life Sci 1980, 26: 1473–1477.
54 Mezei, M, Gulasekharam, V. Liposomes. A selective drug delivery system for the topical route of administration: gel dosage form. J Pharm Pharmacol 1982, 34:473–474.
55 Elsayed, MM, Abdallah, OY, Naggar, VF, Khalafallah, NM. Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen. Pharmazie 2007, 62:133–137.
56 Küchler, S, Radowski, MR, Blaschke, T, Dathe, M, Plendl, J, Haag, R, Schäfer‐Korting, M, Kramer, KD. Nanoparticles for skin penetration enhancement–a comparison of a dendritic core‐multishell‐nanotransporter and solid lipid nanoparticles. Eur J Pharm Biopharm 2009, 71:243–250.
57 Karande, P, Jain, A, Ergun, K, Kispersky, V, Mitragotri, S. Design principles of chemical penetration enhancers for transdermal drug delivery. Proc Natl Acad Sci U S A 2005, 102:4688–4693.
58 Gerber, M, Breytenbach, JC, du Plessis, J. Transdermal penetration of zalcitabine, lamivudine and synthesised N‐acyl lamivudine esters. Int J Pharm 2008, 351:186–193.
59 Jain, MK, Wu, NY, Wray, LV. Drug‐induced phase change in bilayer as possible mode of action of membrane expanding drugs. Nature 1975, 255:494–496.
60 Kumar, P, Batta, R, LaBine, G, Shen, J, Gaspar, K, Docherty, J, Foldvari, M. Stabilization of interferon α
‐2b in a topical cream. Pharm Technol 2009, 33:80–86.
61 Bouwstra, JA, Cheng, K, Gooris, GS, Weerheim, A, Ponec, M. The role of ceramides 1 and 2 in the stratum corneum lipid organization. Biochim Biophys Acta 1996, 1300:177–186.
62 Needham, D, Nunn, RS. Elastic deformation and failure of lipid bilayer membranes containing cholesterol. Biophys J 1990, 58:997–1009.
63 Hamilton, JA, Cordes, EH. Molecular dynamics of lipids in human plasma high density lipoproteins. A high field 13C NMR study. J Biol Chem 1978, 253:5193–5198.
64 Hadgraft, J. Skin deep. Eur J Pharm Biopharm 2004, 58:291–299.
65 Tieleman, DP, Marrink, SJ, Berendsen, HJ. A computer perspective of membranes: molecular dynamics studies of lipid bilayer systems. Biochim Biophys Acta 1997, 1331:235–270.
66 Ash, WL, Stockner, T, MacCallum, JL, Tieleman, DP. Computer modeling of polyleucine‐based coiled coil dimers in a realistic membrane environment: insight into helix‐helix interactions in membrane proteins. Biochemistry 2004, 43:9050–9060.
67 Egberts, E, Marrink, SJ, Berendsen, HJ. Molecular dynamics simulation of a phospholipid membrane. Eur Biophys J 1994, 22:423–436.
68 Smondyrev, AM, Berkowitz, ML. Molecular dynamics simulation of DPPC bilayer in DMSO. Biophys J 1999, 76:2472–2478.
69 Tieleman, DP, Leontiadou, H, Mark, AE, Marrink, SJ. Simulation of pore formation in lipid bilayers by mechanical stress and electric fields. J Am Chem Soc 2003, 125:6382–6383.
70 Kim, EB, Lockwood, N, Chopra, M, Guzmán, O, Abbott, NL, de Pablo, JJ. Interactions of liquid crystal‐forming molecules with phospholipid bilayers studied by molecular dynamics simulations. Biophys J 2005, 89:3141–3158.
71 de Vries, AH, Mark, AE, Marrink, SJ. Molecular dynamics simulation of the spontaneous formation of a small DPPC vesicle in water in atomistic detail. J Am Chem Soc 2004, 126:4488–4489.
72 Marrink, SJ, Tieleman, DP. Molecular dynamics simulation of spontaneous membrane fusion during a cubic‐hexagonal phase transition. Biophys J 2002, 83:2386–2392.
73 Tieleman, DP, Biggin, PC, Smith, GR, Sansom, MS. Simulation approaches to ion channel structure‐function relationships. Q Rev Biophys 2001, 34:473–561.
74 Beckstein, O, Biggin, PC, Bond, P, Bright, JN, Domene, C, Grottesi, A, Holyoake, J, Sansom, MSP. Ion channel gating: insights via molecular simulations. FEBS Lett 2003, 555:85–90.
75 Aqvist, J, Luzhkov, V. Ion permeation mechanism of the potassium channel. Nature 2000, 404:881–884.
76 de Groot, BL, Grubmüller, H. Water permeation across biological membranes: mechanism and dynamics of aquaporin‐1 and GlpF. Science 2001, 294:2353–2357.
77 Chakrabarti, N, Tajkhorshid, E, Roux, B, Pomès, R. Molecular basis of proton blockage in aquaporins. Structure 2004, 12:65–74.
78 Marrink, SJ, Mark, AE. The mechanism of vesicle fusion as revealed by molecular dynamics simulations. J Am Chem Soc 2003, 125:11144–11145.
79 Kollman, P. Free‐energy calculations ‐ applications to chemical and biochemical phenomena. Chem Rev 1993, 93:2395–2417.
80 Northrup, SH, Pear, MR, Lee, CY, McCammon, JA, Karplus, M. Dynamical theory of activated processes in globular proteins. Proc Natl Acad Sci U S A 1982, 79:4035–4039.
81 Mitsutake, A, Sugita, Y, Okamoto, Y. Generalized‐ensemble algorithms for molecular simulations of biopolymers. Biopolymers 2001, 60:96–123.
82 Metropolis, N, Ulam, S. The Monte Carlo method. J Am Stat Assoc 1949, 44:335–341.
83 Hastings, WK. Monte Carlo sampling methods using Markov chains and their applications. Biometrika 1970, 57:97–109.
84 Hills, RD, Lu, L, Voth, GA. Multiscale coarse‐graining of the protein energy landscape. PLoS Comput Biol 2010, 6:e1000827.
85 Chao, SD, Kress, JD, Redondo, A. Coarse‐grained rigid blob model for soft matter simulations. J Chem Phys 2005, 122:234912.
86 Rim, JE, Pinsky, PM, van Osdol, WW. Multiscale modeling framework of transdermal drug delivery. Anals Biomed Eng 2009, 37:1217–1229.
87 Schumm, P, Scoglio, CM, van der Merwe, D. A network model of successive partitioning‐limited solute diffusion through the stratum corneum. J Theor Biol 2010, 262:471–477.
88 Höltje, M, Förster, T, Brandt, B, Engels, T, von Rybinski, W, Höltje, HD. Molecular dynamics simulations of stratum corneum lipid models: fatty acids and cholesterol. Biochim Biophys Acta 2001, 1511:156–167.
89 Van Der Spoel, D, Lindahl, E, Hess, B, Groenhof, G, Mark, AE, Berendsen, HJC. GROMACS: fast, flexible, and free. J Comput Chem 2005, 26:1701–1718.
90 Pandit, SA, Scott, HL. Molecular‐dynamics simulation of a ceramide bilayer. J Chem Phys 2006, 124:14708.
91 Mombelli, E, Morris, R, Taylor, W, Fraternali, F. Hydrogen‐bonding propensities of sphingomyelin in solution and in a bilayer assembly: a molecular dynamics study. Biophys J 2003, 84:1507–1517.
92 Notman, R, den Otter, WK, Noro, MG, Briels, WJ, Anwar, J. The permeability enhancing mechanism of DMSO in ceramide bilayers simulated by molecular dynamics. Biophys J 2007, 93:2056–2068.
93 Das, C, Noro, MG, Olmsted, PD. Simulation studies of stratum corneum lipid mixtures. Biophys J 2009, 97:1941–1951.
94 Das, C, Olmsted, PD, Noro, MG. Water permeation through stratum corneum lipid bilayers from atomistic simulations. Soft Matter 2009, 5:4549–4555.
95 Bouwstra, JA, Dubbelaar, FE, Gooris, GS, Ponec, M. The lipid organisation in the skin barrier. Acta Derm Venereol Suppl 2000, 208:23–30.