title: Glycan-mediated uptake in urothelial primary cells: Perspectives for improved intravesical drug delivery in urinary tract infections.
abstract: Urinary tract infections (UTIs) are among the most common bacterial infections. Despite a wide range of therapeutic options, treatment success is compromised by multiresistance and the efficient mechanism of tissue colonization of uropathogenic Escherichia coli (UPEC). In advanced drug delivery systems, a similar, glycan-mediated targeting mechanism may be realized by conjugating the drug to a plant lectin. This may lead to the drug being more efficiently accumulated at the desired site of action, the bacterial reservoirs. In this study, we aimed at elucidating the potential of this biorecognitive approach. Glycan-triggered interaction cascades and uptake processes of several plant lectins with distinct carbohydrate specificities were characterized using single cells and monolayer culture. Due to pronounced cytoadhesive and cytoinvasive properties, wheat germ agglutinin (WGA) emerged as a promising targeter in porcine urothelial primary cells. The lectin-cell interaction proved highly stabile in artificial urine, simulating the conditions in actual application. Colocalisation studies with internalized WGA and lens culinaris agglutinin (LCA) revealed that intracellular accumulation sites were largely identical for GlcNAc- and Mannose-specific lectins. This indicates that WGA-mediated delivery may indeed constitute a potent tool to reach bacteria taken up via a FimH-triggered invasion process. Existing pitfalls in intravesical treatment schedules may soon be overcome.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. Electronic address: clara.maria.pichl@univie.ac.at.
authors.forename: Clara Maria
authors.initials: CM
authors.lastname: Pichl
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria.
authors.forename: Sophie
authors.initials: S
authors.lastname: Feilhauer
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Schwaigerlehner
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. Electronic address: franz.gabor@univie.ac.at.
authors.forename: Franz
authors.initials: F
authors.lastname: Gabor
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. Electronic address: michael.wirth@univie.ac.at.
authors.forename: Michael
authors.initials: M
authors.lastname: Wirth
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. Electronic address: neuc@zhaw.ch.
authors.forename: Lukas
authors.initials: L
authors.lastname: Neutsch
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D016503:Drug Delivery Systems; D037102:Lectins / Q000008:administration & dosage / Q000378:metabolism*; D037121:Plant Lectins / Q000008:administration & dosage / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D013552:Swine; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism; D014552:Urinary Tract Infections / Q000188:drug therapy; D019459:Urothelium / Q000166:cytology / Q000378:metabolism*; D014909:Wheat Germ Agglutinins / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D037102:Lectins; D037121:Plant Lectins; D011134:Polysaccharides; D014909:Wheat Germ Agglutinins; C033619:lentil lectin
keywords: Antibiotic; Instillation; Internalization; Lectin; UPEC; Urinary tract infection