Enabling noninvasive systemic delivery of the Kv1.3-blocking peptide HsTX1[R14A] via the buccal mucosa

Liang Jin, Ben J. Boyd, Ian C. Larson, Michael W. Pennington, Raymond S. Norton, Joseph A. Nicolazzo

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)


The peptide HsTX1[R14A] is a potent and selective blocker of the voltage-gated potassium channel Kv1.3, a well-recognized therapeutic target for autoimmune diseases. To overcome the poor oral absorption and consequent need for regular injections, the potential of the buccal mucosa for systemic delivery of HsTX1[R14A] was investigated. For in vitro studies, FITC-HsTX1[R14A] and HsTX1[R14A], in solution or formulated in a mucoadhesive chitosan–based gel (3%, w/v) with or without cetrimide (5%, w/w), were applied to porcine buccal epithelium mounted between Ussing chambers and buccal mucosal permeation assessed. HsTX1[R14A] was also administered to Swiss outbred mice at a dose of 10 mg/kg in the same formulations. In vitro, administration of FITC-HsTX1[R14A] and HsTX1[R14A] in the chitosan gel containing cetrimide resulted in detectable buccal permeation with 0.75% and 0.58%, respectively, of the applied dose appearing in the receptor chamber over 5 h. After buccal administration to mice, HsTX1[R14A] was detected in plasma, with the presence of cetrimide in the gel further enhancing plasma exposure, with area under the plasma concentration-time curve values of 77.9 ± 9.7 and 31.0 ± 2.3 nM·h, respectively. The buccal mucosa is a promising alternative administration route for the systemic delivery of HsTX1[R14A] for the treatment of autoimmune diseases.

Original languageEnglish
Pages (from-to)2173-2179
Number of pages7
JournalJournal of Pharmaceutical Sciences
Issue number7
Publication statusPublished - 1 Jul 2016


  • absorption
  • chitosan
  • mucosal delivery
  • peptides
  • permeability

Cite this