Preference of Aerosolized Pirfenidone to Oral Intake: An Experimental Model of Pulmonary Fibrosis by Paraquat.

Abstract

Inhalation drug delivery is a fast, effective, and safe route of delivering medication directly to the lungs. Thanks to the large surface area and highly vascularized epithelium in lung, pulmonary drug delivery has been considered as an effective route to deliver drugs to the systemic circulation. Pirfenidone (PF), an oral antifibrotic agent, has been shown to slow down the progression of the lung fibrosis. Inhalation or intrapulmonary delivery of PF appears to be a good alternative to optimize drug delivery and minimize the dosage, adverse and nonspecific effects. Pulmonary fibrosis was induced by paraquat in rats. After induction of fibrosis, PF was administered via oral and inhalation routes for 14 consecutive days. The efficacy of oral and inhalation routes were compared by evaluating morphological changes, hydroxyproline content, tissue oxidative stress parameters, and proinflammatory and profibrotic genes expression including transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), tissue inhibitor of metalloproteinase 1 (TIMP-1), and matrix metalloproteinase 2 (MMP-2) genes. The results showed similar therapeutic effects and efficacy for both inhalation and oral routes; however, the dose of inhalation route was much less than that for oral administration. In conclusion, PF offers great potential as an inhalation delivery formulation for treatment of pulmonary fibrosis.