Novel dry powder formulation of ovalbumin for development of COPD-like animal model: Physicochemical characterization and biomarker profiling in rats
Novel dry powder formulation of ovalbumin for development of COPD-like animal model: Physicochemical characterization and biomarker profiling in rats
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DOI：
10.1016/j.ejps.2009.04.002
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发表时间：
2009-06-28
影响因子：
4.6
通讯作者：
Yamada, Shizuo
中科院分区：
文献类型：
--
作者：
Misaka, Shingen;Sato, Hideyuki;Yamada, Shizuo
本研究旨在开发一种新型的卵清蛋白干粉吸入系统（OVA-DPI），用于制备慢性阻塞性肺疾病的实验动物模型，以辅助药物发现。用气流粉碎机制备的OVA-DPI显示出高的分散性和从胶囊中的释放，如通过级联冲击器评价的。基于采用扫描电子显微镜、UPLC/ESI-MS分析、粉末X射线衍射和TG/DTA分析的长期稳定性研究的结果，发现在室温下储存的OVA-DPI可稳定超过3年，如无显著降解和晶体多晶型所证明。OVA致敏大鼠腹腔注射OVA-DPI后，浸润的粒细胞增加11倍，尤其是中性粒细胞，这可能是严重哮喘/COPD症状的特征。在监测的所有血浆生物标志物中，髓过氧化物酶活性和乳酸脱氢酶渗漏到血液中似乎是该模型中肺损伤的敏感指标。另外，OVA-DPI可引起LDH双相升高，在抗原攻击后3 h和24 h达到高峰，提示OVA-DPI可引起急性和迟发性炎症反应。基于这些发现，OVA-DPI可用于开发实验性哮喘/COPD模型的有用和可重复的研究工具。(C)2009爱思唯尔有限公司版权所有。
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 24 h 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. (C) 2009 Elsevier B.V. All rights reserved.