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Respirable dry powder formulation of bleomycin for developing a pulmonary fibrosis animal model.

Abstract
The main purpose of the present study was to develop a respirable powder (RP) formulation of bleomycin (BLM) as a research tool for developing a pulmonary fibrosis animal model. The BLM-RP was prepared with a jet-milling system, the physicochemical properties of which were characterized focusing on morphology, stability, particle size distribution, and inhalation performance. Under an accelerated condition, the BLM-RP was superior to BLM solution in terms of its stability. Cascade impactor analyses demonstrated high inhalation performance with emitted dose and fine particle fraction of approximately 99% and 46%, respectively. Intratracheal administration of the BLM-RP (3 mg BLM/kg) in rats led to significant increases in collagen production and recruitment of inflammatory cells in lung by approximately 1.5- and 29-fold, respectively. The collagen overexpression was consistent with the results from picrosirius red staining of lung tissues in the rats treated with BLM-RP. Inhaled tranilast (TL; 100 μg/rat), an antifibrotic agent, could ameliorate inflammatory/fibrotic responses with reductions of recruited inflammatory cells and collagen content by 32% and 59%, respectively, validating the pulmonary fibrosis animal model. From these findings, the BLM-RP with improved stability could be a beneficial research tool for developing a pulmonary fibrosis model in drug discovery for antifibrotic drug candidates.
AuthorsYosuke Aoki, Yoshiki Kojo, Shizuo Yamada, Satomi Onoue
JournalJournal of pharmaceutical sciences (J Pharm Sci) Vol. 101 Issue 6 Pg. 2074-81 (Jun 2012) ISSN: 1520-6017 [Electronic] United States
PMID22388976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Wiley Periodicals, Inc.
Chemical References
  • Powders
  • Bleomycin
Topics
  • Animals
  • Bleomycin (chemistry, toxicity)
  • Disease Models, Animal
  • Male
  • Powders
  • Pulmonary Fibrosis (chemically induced)
  • Rats
  • Rats, Sprague-Dawley

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