Acrylate-Tethering Drug Carrier: Covalently Linking Carrier to Biological Surface and Application in the Treatment of Helicobacter pylori Infection

作者：Tachaprutinun Amornset; Pan In Porntip; Samutprasert Pawatsanai; Banlunara Wijit; Chaichanawongsaroj Nuntaree; Wanichwecharungruang Supason^*

来源：Biomacromolecules, 2014, 15(11): 4239-4248.

DOI：10.1021/bm501261818

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.

• 出版日期2014-11