Delivery of Imatinib-Incorporated Nanoparticles into Lungs Suppresses the Development of Monocrotaline-Induced Ulmonary Arterial Hypertension

Satoshi Akagi, Kazufumi Nakamura, Daiji Miura, Yukihiro Saito, Hiromi Matsubara, Aiko Ogawa, Tetsuya Matoba, Kensuke Egashira, Hiroshi Ito

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Platelet–derived growth factor (PDGF) is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Imatinib, a PDGF-receptor tyrosine kinase inhibitor, improved hemodynamics, but serious side effects and drug discontinuation are common when treating PAH. A drug delivery system using nanoparticles (NPs) enables the reduction of side effects while maintaining the effects of the drug. We examined the efficacy of imatinib-incorporated NPs (Ima-NPs) in a rat model and in human PAH-pulmonary arterial smooth muscle cells (PASMCs). Rats received a single intratracheal administration of PBS, FITC-NPs, or Ima-NPs immediately after monocrotaline injection. Three weeks after monocrotaline injection, intratracheal administration of Ima-NPs suppressed the development of pulmonary hypertension, small pulmonary artery remodeling, and right ventricular hypertrophy in the rat model of monocrotaline-induced PAH. We also examined the effects of imatinib and Ima-NPs on PDGF-induced proliferation of human PAH-PASMCs by 3H-thymidine incorporation. Imatinib and Ima-NPs significantly inhibited proliferation after 24 hours of treatment. Ima-NPs significantly inhibited proliferation compared with imatinib at 24 hours after removal of these drugs. Delivery of Ima-NPs into lungs suppressed the development of MCT-induced PAH by sustained antiproliferative effects on PASMCs.

Original languageEnglish
Pages (from-to)354-359
Number of pages6
JournalInternational heart journal
Volume56
Issue number3
DOIs
Publication statusPublished - Apr 27 2015

Keywords

  • Drug delivery system
  • Nanomedicine
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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