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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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
Volume105
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • absorption
  • chitosan
  • mucosal delivery
  • peptides
  • permeability

Cite this

@article{425f6f7cd1114fbd9ca1fef88e66e75e,
title = "Enabling noninvasive systemic delivery of the Kv1.3-blocking peptide HsTX1[R14A] via the buccal mucosa",
abstract = "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.",
keywords = "absorption, chitosan, mucosal delivery, peptides, permeability",
author = "Liang Jin and Boyd, {Ben J.} and Larson, {Ian C.} and Pennington, {Michael W.} and Norton, {Raymond S.} and Nicolazzo, {Joseph A.}",
year = "2016",
month = "7",
day = "1",
doi = "10.1016/j.xphs.2016.05.008",
language = "English",
volume = "105",
pages = "2173--2179",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "Elsevier",
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Enabling noninvasive systemic delivery of the Kv1.3-blocking peptide HsTX1[R14A] via the buccal mucosa. / Jin, Liang; Boyd, Ben J.; Larson, Ian C.; Pennington, Michael W.; Norton, Raymond S.; Nicolazzo, Joseph A.

In: Journal of Pharmaceutical Sciences, Vol. 105, No. 7, 01.07.2016, p. 2173-2179.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Enabling noninvasive systemic delivery of the Kv1.3-blocking peptide HsTX1[R14A] via the buccal mucosa

AU - Jin, Liang

AU - Boyd, Ben J.

AU - Larson, Ian C.

AU - Pennington, Michael W.

AU - Norton, Raymond S.

AU - Nicolazzo, Joseph A.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

AB - 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.

KW - absorption

KW - chitosan

KW - mucosal delivery

KW - peptides

KW - permeability

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U2 - 10.1016/j.xphs.2016.05.008

DO - 10.1016/j.xphs.2016.05.008

M3 - Article

VL - 105

SP - 2173

EP - 2179

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

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