Novel dry powder formulation of ovalbumin for development of COPD-like animal model: Physicochemical characterization and biomarker profiling in rats.
This study was directed toward the development of novel ovalbumin dry powder inhalation system (OVA-DPI) for preparing experimental animal models of chronic obstructive pulmonary disease, with the aim of aiding the drug discovery. OVA-DPI, prepared with jet mill, showed high dispersion and emission from capsule as evaluated by cascade impactor. Based on the results from long term stability studies employing scanning electron microscopy, UPLC/ESI-MS analysis, powder X-ray diffraction and TG/DTA analyses, the OVA-DPI, stored at room temperature, was found to be stable for more than 3 years as evidenced by no significant degradation and crystal polymorphism. Intratracheal administration of OVA-DPI in OVA-sensitized rats resulted in 11-fold increase of infiltrated granulocytes, especially neutrophil, which would be characteristics of severe asthma/COPD symptoms. Of all plasma biomarkers monitored, myeloperoxidase activity and lactate dehydrogenase leakage into blood seemed to be sensitive indicators of lung injury in this model. In addition, biphasic increase of LDH was observed with peak responses at 3 and 24h after antigen challenge, suggesting that OVA-DPI could cause both acute and delayed inflammatory reactions. Upon these findings, OVA-DPI can be useful and reproducible research tool for the development of experimental asthma/COPD model.
Misaka
Shingen
S
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Sato
Hideyuki
H
Yamauchi
Yukinori
Y
Onoue
Satomi
S
Yamada
Shizuo
S
D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004055:Differential Thermal Analysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009391:Nephelometry and Turbidimetry; D010047:Ovalbumin / Q000008:administration & dosage*; D010316:Particle Size; D009195:Peroxidase / Q000378:metabolism; D011208:Powders; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage*; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D015415:Biomarkers; D011208:Powders; D017382:Reactive Oxygen Species; D015842:Serine Proteinase Inhibitors; D010047:Ovalbumin; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase