Transdermal delivery of a readthrough-inducing drug: A new approach of gentamicin administration for the treatment of nonsense mutation-mediated disorders

Masataka Shiozuka, Akira Wagatsuma, Tadafumi Kawamoto, Hiroyuki Sasaki, Kenichi Shimada, Yoshikazu Takahashi, Yoshiaki Nonomura, Ryoichi Matsuda

研究成果: Contribution to journalArticle査読

14 被引用数 (Scopus)

抄録

To induce the readthrough of premature termination codons, aminoglycoside antibiotics such as gentamicin have attracted interest as potential therapeutic agents for diseases caused by nonsense mutations. The transdermal delivery of gentamicin is considered unfeasible because of its low permeability through the dermis. However, if the skin permeability of gentamicin could be improved, it would allow topical application without the need for systemic delivery. In this report, we demonstrated that the skin permeability of gentamicin increased with the use of a thioglycolate-based depilatory agent. After transdermal administration, the readthrough activity in skeletal muscle, as determined using a lacZ/luc reporter system, was found to be equivalent to systemic administration when measured in transgenic mice. Transdermally applied gentamicin was detected by liquid chromatography-tandem mass spectrometry in the muscles and sera of mice only after depilatory agent-treatment. In addition, expansion of the intercellular gaps in the basal and prickle-cell layers was observed by electron microscopy only in the depilatory agent-treated mice. Depilatory agent-treatment may be useful for the topical delivery of readthough-inducing drugs for the rescue of nonsense mutation-mediated genetic disorders. This finding may also be applicable for the transdermal delivery of other pharmacologically active molecules.

本文言語英語
ページ(範囲)463-470
ページ数8
ジャーナルJournal of biochemistry
147
4
DOI
出版ステータス出版済み - 4 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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