title: Acrylate-tethering drug carrier: covalently linking carrier to biological surface and application in the treatment of Helicobacter pylori infection.
abstract: The development of carriers to sustain drugs at stomach surface is an attractive strategy to increase drug bioavailability locally and systematically. So far, the only reported carrier that can form a covalent bond with mucus, the thiolated carrier, relies on a reversible disulfide exchange reaction between thiols on the carrier and disulfide bridges on the mucus. Here we show the design and fabrication of a cellulose carrier with tethering acrylate groups (denoted here as clickable carrier) that, under a nontoxic condition, can efficiently react with thiols on biomaterials in situ through the thermodynamically driven and kinetically probable Michael thiol-ene click reaction. Here we show the attachments of the clickable carriers to a mucin protein, a surface of human laryngeal carcinoma cells, and a surface of a fresh porcine stomach. We also show that the required thiol moieties can be generated in situ by reducing existing cystine disulfide bridges with either the edible vitamin C or the relatively nontoxic tris(2-carboxyethyl) phosphine. Comparing to a control carrier, the clickable carrier can increase some drug concentrations in an ex vivo stomach tissue, and improve the Helicobacter pylori treatment in infected C57BL/6 mice.
authors.affiliation: Department of Chemistry, Faculty of Science, ‡Department of Pathology, Faculty of Veterinary Science, §Department of Transfusion Medicine, Faculty of Allied Health Sciences, and ∥The Center of Excellence on Petrochemical and Materials Technology, Chulalongkorn University , Bangkok, Thailand.
authors.forename: Amornset
authors.initials: A
authors.lastname: Tachaprutinun
authors.forename: Porntip
authors.initials: P
authors.lastname: Pan-In
authors.forename: Pawatsanai
authors.initials: P
authors.lastname: Samutprasert
authors.forename: Wijit
authors.initials: W
authors.lastname: Banlunara
authors.forename: Nuntaree
authors.initials: N
authors.lastname: Chaichanawongsaroj
authors.forename: Supason
authors.initials: S
authors.lastname: Wanichwecharungruang
mesh_terms: D000179:Acrylates / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D013499:Surface Properties / Q000187:drug effects; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000179:Acrylates; D004337:Drug Carriers; C036658:acrylic acid