Spermine with Sodium Taurocholate Enhances Pulmonary Absorption of Macromolecules in Rats

Masateru Miyake, Takanori Minami, Masato Maruyama, Tadashi Mukai, Kazutaka Higaki

Research output: Contribution to journalArticlepeer-review

Abstract

The improvement effect of the combined use of spermine (SPM), a polyamine, with sodium taurocholate (STC) on the pulmonary drug absorption was investigated utilizing poorly absorbable drugs with various molecular sizes in rats. The pulmonary absorption of rebamipide, a low molecular but poorly absorbable drug after oral administration, was significantly improved by the combined use of SPM with STC (SPM-STC formulation), while poly- L-lysine did not show a significant change in rebamipide absorption from the lungs. Furthermore, the safety of the SPM-STC formulation for the lungs was assessed in rats by the histopathological study and any local toxicity was not observed while poly-L-lysine, a typical chemical causing the toxicity for the epithelial cells, provided several histopathological changes. In addition, the SPM-STC formulation significantly improved the pulmonary absorption of fluorescein isothiocyanate dextran 4 (FD-4, Mw ca 4000) and interferon-α (IFN-α, Mw ca 25,000) as well. Our present results clearly indicated that the SPM-STC formulation significantly improved the pulmonary absorption of poorly absorbable small and large molecular drugs without any harmful effects on the lungs. Therefore, the SPM-STC formulation would be a useful one for the pulmonary absorption of drugs, specifically macromolecular ones, which are very difficult to be absorbed after oral administration.

Original languageEnglish
Pages (from-to)3464-3470
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume110
Issue number10
DOIs
Publication statusPublished - Oct 2021

Keywords

  • Absorption enhancer
  • Histopathology
  • Local toxicity
  • Macromolecules
  • Pulmonary absorption
  • Sodium taurocholate
  • Spermine

ASJC Scopus subject areas

  • Pharmaceutical Science

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