title: Efficient mucosal delivery of optical contrast agents using imidazole-modified chitosan.
abstract: The clinical applicability of antibodies and plasmonic nanosensors as topically applied, molecule-specific optical diagnostic agents for noninvasive early detection of cancer and precancer is severely limited by our inability to efficiently deliver macromolecules and nanoparticles through mucosal tissues. We have developed an imidazole-functionalized conjugate of the polysaccharide chitosan (chitosan-IAA) to enhance topical delivery of contrast agents, ranging from small molecules and antibodies to gold nanoparticles up to 44 nm in average diameter. Contrast agent uptake and localization in freshly resected mucosal tissues was monitored using confocal microscopy. Chitosan-IAA was found to reversibly enhance mucosal permeability in a rapid, reproducible manner, facilitating transepithelial delivery of optical contrast agents. Permeation enhancement occurred through an active process, resulting in the delivery of contrast agents via a paracellular or a combined paracellular/transcellular route depending on size. Coadministration of epidermal growth factor receptor-targeted antibodies with chitosan-IAA facilitated specific labeling and discrimination between paired normal and malignant human oral biopsies. Together, these data suggest that chitosan-IAA is a promising topical permeation enhancer for mucosal delivery of optical contrast agents.
authors.affiliation: The University of Texas at Austin, Department of Biomedical Engineering, Austin, Texas 78712, USA.
authors.forename: Bilal
authors.initials: B
authors.lastname: Ghosn
authors.forename: Anne L
authors.initials: AL
authors.lastname: van de Ven
authors.forename: Justina
authors.initials: J
authors.lastname: Tam
authors.forename: Ann
authors.initials: A
authors.lastname: Gillenwater
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Sokolov
authors.forename: Rebecca
authors.initials: R
authors.lastname: Richards-Kortum
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Roy
mesh_terms: D000287:Administration, Topical; D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry*; D018613:Microscopy, Confocal; D009061:Mouth Mucosa / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism; D010539:Permeability; D020127:Recovery of Function; D001743:Urinary Bladder / Q000378:metabolism
chemical_list: D003287:Contrast Media; D007093:Imidazoles; C029899:imidazole; D048271:Chitosan; D066246:ErbB Receptors