Novel Strategy for the Systemic Delivery of Furosemide Based on a New Drug Transport Mechanism

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  • Kimura Shunsuke
    Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts
  • Kiriyama Akiko
    Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts
  • Nishimura Erika
    Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts
  • Sakata Shiori
    Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts
  • Inoue Daisuke
    School of Pharmacy, Shujitsu University
  • Furubayashi Tomoyuki
    School of Pharmacy, Shujitsu University
  • Yutani Reiko
    Department of Pharmaceutical Technology, Kobe Pharmaceutical University
  • Tanaka Akiko
    Department of Pharmaceutical Technology, Kobe Pharmaceutical University
  • Kusamori Kosuke
    Department of Biopharmaceutics, Kyoto Pharmaceutical University
  • Katsumi Hidemasa
    Department of Biopharmaceutics, Kyoto Pharmaceutical University
  • Iga Katsumi
    Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts
  • Yamamoto Akira
    Department of Biopharmaceutics, Kyoto Pharmaceutical University
  • Sakane Toshiyasu
    Department of Pharmaceutical Technology, Kobe Pharmaceutical University

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Abstract

<p>We reported a novel transport mechanism of curcumin, independent of improved solubility, which involved direct contact of amorphous solid particles with the cell membrane. This mechanism has potential as a novel systemic delivery system of poorly water-soluble drugs. In this study, the transport mechanism of furosemide (FUR), which is transported by the same novel mechanism, was examined. In vitro cell permeation studies under air-interface conditions (AICs) revealed that the permeation from powders sprayed on cell monolayers was significantly higher than that under liquid-covered conditions (LCCs) from their solutions. The permeation from amorphous solid particles was faster than that from crystals. Similar results were derived from in vitro studies using an artificial membrane, with which the permeation of FUR could be examined without water. These findings clearly indicated that the transport mechanism of FUR is the same as that of curcumin. For the application of this new transport mechanism, the in vivo absorption of FUR was examined after pulmonary insufflation, which allows the solid particles to make direct contact with the epithelial cells. Pulmonary absorption of FUR from the amorphous powder was almost complete and was faster than that after intragastric administration of the solution, suggesting that FUR was absorbed from the lung by the same mechanism as the in vitro study. This new transport mechanism, which is independent of water dissolution, could be exploited to develop a novel delivery system for poorly water-soluble drugs, using pulmonary powder inhalation.</p>

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