Pulmonary delivery of the Kv1.3-blocking peptide HsTX1[R14A] for the treatment of autoimmune diseases

Liang Jin, Qi (Tony) Zhou, Hak-Kim Chan, Ian C. Larson, Michael W. Pennington, Rodrigo A.V. Morales, Ben J. Boyd, Raymond S. Norton, Joseph A. Nicolazzo

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)


HsTX1[R14A] is a potent and selective Kv1.3 channel blocker peptide with the potential to treat autoimmune diseases. Given the typically poor oral bioavailability of peptides, we evaluated pulmonary administration of HsTX1[R14A] in rats as an alternative route for systemic delivery. Plasma concentrations of HsTX1[R14A] were measured by liquid chromatography coupled with tandem mass spectrometry in rats receiving intratracheal administration of HsTX1[R14A] in solution (1-4 mg/kg) or a mannitol-based powder (1 mg/kg) and compared with plasma concentrations after intravenous administration (2 mg/kg). HsTX1[R14A] stability in rat plasma and lung tissue was also determined. HsTX1[R14A] was more stable in plasma than in lung homogenate, with more than 90% of the HsTX1[R14A] remaining intact after 5 h, compared with 40.5% remaining in lung homogenate. The terminal elimination half-life, total clearance, and volume of distribution of HsTX1[R14A] after intravenous administration were 79.6 ± 6.5 min, 8.3 ± 0.6 mL/min/kg, and 949.8 ± 71.0 mL/kg, respectively (mean ± SD). After intratracheal administration, HsTX1[R14A] in solution and dry powder was absorbed to a similar degree, with absolute bioavailability values of 39.2 ± 5.2% and 44.5 ± 12.5%, respectively. This study demonstrated that pulmonary administration is a promising alternative for systemically delivering HsTX1[R14A] for treating autoimmune diseases.

Original languageEnglish
Pages (from-to)650-656
Number of pages7
JournalJournal of Pharmaceutical Sciences
Issue number2
Publication statusPublished - 1 Feb 2016


  • epithelial delivery
  • peptides
  • pharmacokinetics
  • pulmonary absorption
  • pulmonary drug delivery

Cite this