title: Glycosylation facilitates transdermal transport of macromolecules.
abstract: Stratum corneum, the outermost layer of skin, allows transport of only low-molecular weight (<500) lipophilic solutes. Here, we report a surprising finding that avicins (Avs), a family of naturally occurring glycosylated triterpenes with a molecular weight > 2,000, exhibit skin permeabilities comparable to those of small hydrophobic molecules, such as estradiol. Systematic fragmentation of the Av molecule shows that deletion of the outer monoterpene results in a 62% reduction in permeability, suggesting an important role for this motif in skin permeation. Further removal of the tetrasaccharide residue results in a further reduction of permeability by 79%. These results, taken in sum, imply that synergistic effects involving both hydrophobic and hydrophilic residues may hold the key in facilitating translocation of Avs across skin lipids. In addition to exhibiting high permeability, Avs provided moderate enhancements of skin permeability of estradiol and polysaccharides, including dextran and inulin but not polyethylene glycol.
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pino
authors.forename: Jordan U
authors.initials: JU
authors.lastname: Gutterman
authors.forename: Daniel
authors.initials: D
authors.lastname: Vonwil
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
authors.forename: V Prasad
authors.initials: VP
authors.lastname: Shastri
mesh_terms: D000327:Adsorption; D000818:Animals; D001692:Biological Transport; D002152:Calorimetry, Differential Scanning; D020405:Dermis / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances / Q000378:metabolism*; D008958:Models, Molecular; D000442:Octanols / Q000737:chemistry; D012503:Saponins / Q000737:chemistry / Q000378:metabolism; D012869:Skin Absorption; D034421:Sus scrofa; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D046911:Macromolecular Substances; D000442:Octanols; D012503:Saponins; C478446:avicin G; D014867:Water; D004958:Estradiol; C478445:avicin D