title: Description of transdermal transport of hydrophilic solutes during low-frequency sonophoresis based on a modified porous pathway model.
abstract: Application of low-frequency ultrasound has been shown to increase skin permeability, thereby facilitating delivery of macromolecules (low-frequency sonophoresis). In this study, we sought to determine a theoretical description of transdermal transport of hydrophilic permeants induced by low-frequency sonophoresis. Parameters such as pore size distribution, absolute porosity, and dependence of effective tortuosity on solute characteristics were investigated. Pig skin was exposed to low-frequency ultrasound at 58 kHz to achieve different skin resistivities. Transdermal delivery of four permeants [mannitol, luteinizing hormone releasing hormone (LHRH), inulin, dextran] in the presence and absence of ultrasound was measured. The porous pathway model was modified to incorporate the permeant characteristics into the model and to achieve a detailed understanding of the pathways responsible for hydrophilic permeant delivery. The slopes of the log kp(p) versus log R graphs for individual solutes changed with solute molecular area, suggesting that the permeability-resistivity correlation for each permeant is related to its size. The tortuosity that a permeant experiences within the skin also depends on its size, where larger molecules experience a less tortuous path. With the modified porous pathway model, the effective tortuosities and skin porosity were calculated independently. The results of this study show that low-frequency sonophoresis creates pathways for permeant delivery with a wide range of pore sizes. The optimum pore size utilized by solutes is related to their molecular radii.
authors.affiliation: Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, California 93106, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Tezel
authors.forename: Ashley
authors.initials: A
authors.lastname: Sens
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000279:Administration, Cutaneous; D000465:Algorithms; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D004058:Diffusion; D005079:Excipients; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007444:Inulin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008051:Lipid Bilayers; D008353:Mannitol / Q000008:administration & dosage / Q000493:pharmacokinetics; D008954:Models, Biological; D008970:Molecular Weight; D016062:Porosity; D012869:Skin Absorption / Q000502:physiology*; D013552:Swine; D014465:Ultrasonics
chemical_list: D003911:Dextrans; D005079:Excipients; D008051:Lipid Bilayers; D007987:Gonadotropin-Releasing Hormone; D008353:Mannitol; D007444:Inulin