ovalbumin and pirfenidone

Topics: Alveolitis, Extrinsic Allergic; Animals; Asthma; Dexamethasone; Inflammation; Macrophages; Male; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Phenotype; Pneumonia; Rats; Rats, Wistar

Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method.. Spray-dried PFD (SD/PFD) was prepared by spray-drying with L-leucine, and the physicochemical properties and efficacy in an antigen-sensitized airway inflammation model were assessed. A pharmacokinetic study was also conducted after intratracheal and oral administration of PFD formulations.. Regarding powder characterization, SD/PFD had dimpled surface with the mean diameter of 1.793 μm. In next generation impactor analysis, SD/PFD demonstrated high in vitro inhalation performance without the need of carrier particles, and the fine particle fraction of SD/PFD was calculated to be 62.4%. Insufflated SD/PFD (0.3 mg-PFD/rat) attenuated antigen-evoked inflammatory events in the lung, including infiltration of inflammatory cells and myeloperoxidase activity. Systemic exposure level of PFD after insufflation of SD/PFD at the pharmacologically effective dose was 600-fold lower than that after oral administration of PFD at the phototoxic dose.. SD/PFD would be suitable for inhalation, and the utilization of an RP system with SD/PFD would provide a safer medication compared with oral administration of PFD.

Topics: Administration, Inhalation; Administration, Oral; Aerosols; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Chromatography, Liquid; Desiccation; Disease Models, Animal; Drug Compounding; Male; Ovalbumin; Particle Size; Peroxidase; Pneumonia; Powders; Pyridones; Rats, Sprague-Dawley; Spectrometry, Mass, Electrospray Ionization; Technology, Pharmaceutical

Pirfenidone was administered to sensitized Brown Norway rats prior to a series of ovalbumin challenges. Airway hyperresponsiveness, inflammatory cell infiltration, mucin and collagen content, and the degree of epithelium and smooth muscle staining for TGF-beta were examined in control, sensitized, and sensitized/challenged rats fed a normal diet or pirfenidone diet. Pirfenidone had no effect on airway hyperresponsiveness, but reduced distal bronchiolar cell infiltration and proximal and distal mucin content. Statistical analysis showed that the control group and sensitized/challenged pirfenidone diet group TGF-beta staining intensity scores were not significantly different from isotype controls, but that the staining intensity scores for the sensitized/challenged normal diet group was significantly different from isotype controls. These results suggest that pirfenidone treatment is effective in reducing some of the components of acute inflammation induced by allergen challenge.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Bronchi; Bronchial Hyperreactivity; Bronchial Provocation Tests; Collagen; Disease Models, Animal; Inflammation; Lung; Male; Mucins; Muscle, Smooth; Ovalbumin; Pyridones; Random Allocation; Rats; Rats, Inbred BN; Respiratory Mucosa; Transforming Growth Factor beta

We investigated the therapeutic potential of a newly developed antifibrotic agent, pirfenidone, to regulate airway remodeling and the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenge. Administration of pirfenidone after sensitization but during the period of ovalbumin challenge significantly prevented the development of airway hyperresponsiveness and prevented eosinophil and lymphocyte accumulation in the airways. IL-4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid and ovalbumin-specific serum IgE antibody levels were also significantly reduced. Treatment with pirfenidone significantly reduced transforming growth factor-beta1 and platelet-derived growth factor levels in bronchoalveolar lavage fluid. Pirfenidone reduced the expression of transforming growth factor-beta1, the development of goblet cell hyperplasia and subepithelial collagenization, and the increases in contractile elements in the lung. These data indicate that pirfenidone may play an important role in the treatment of asthma and has the potential reduce or prevent airway remodeling.

Topics: Allergens; Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cell Proliferation; Cytokines; Eosinophils; Goblet Cells; Hyperplasia; Immunoglobulin E; Interleukin-13; Interleukin-4; Interleukin-5; Leukocytes, Mononuclear; Lymphocytes; Mice; Mice, Inbred BALB C; Ovalbumin; Platelet-Derived Growth Factor; Pyridones; Transforming Growth Factor beta; Transforming Growth Factor beta1