title: Biomimickry of UPEC Cytoinvasion: A Novel Concept for Improved Drug Delivery in UTI.
abstract: Urinary tract infections (UTIs) are among the most common bacterial infections. In an increasing number of cases, pathogen (multi-)resistance hampers durable treatment success via the standard therapies. On the functional level, the activity of urinary excreted antibiotics is compromized by the efficient tissue colonization mechanism of uropathogenic Escherichia coli (UPEC). Advanced drug delivery systems aim at exploiting a glycan-mediated targeting mechanism, similar to the UPEC invasion pathway, to increase bioavailability. This may be realized by conjugation of intravesically applied drugs or drug carriers to chosen plant lectins. Higher local drug concentrations in or nearby bacterial reservoirs may be gained, with higher chances for complete eradication. In this study, preliminary parameters to clarify the potential of this biorecognitive approach were evaluated. Glycan-triggered interaction cascades and uptake processes of several plant lectins with distinct carbohydrate specificities were characterized, and wheat germ agglutinin (WGA) could be identified as the most promising targeter for crossing the urothelial membrane barrier. In partially differentiated primary cells, intracellular accumulation sites were largely identical for GlcNAc- and Mannose-specific lectins. This indicates that WGA-mediated delivery may also enter host cells via the FimH-dependent uptake pathway.
authors: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. clara.maria.pichl@univie.ac.at.
authors: Clara Maria
authors: CM
authors: Pichl
authors: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. bernhard.dunkl@aon.at.
authors: Bernhard
authors: B
authors: Dunkl
authors: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. bernhard.brauner@gmx.at.
authors: Bernhard
authors: B
authors: Brauner
authors: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. franz.gabor@univie.ac.at.
authors: Franz
authors: F
authors: Gabor
authors: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. michael.wirth@univie.ac.at.
authors: Michael
authors: M
authors: Wirth
authors: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstr. 14, 1090 Vienna, Austria. lukas.neutsch@tuwien.ac.at.
authors: Lukas
authors: L
authors: Neutsch
keywords: UPEC; WGA; drug delivery; instillation; lectin; urinary tract infection