Stable dry powder inhaler formulation of tranilast attenuated antigen-evoked airway inflammation in rats
Stable dry powder inhaler formulation of tranilast attenuated antigen-evoked airway inflammation in rats
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DOI：
10.1016/j.ejpb.2010.11.005
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发表时间：
2011-01-01
影响因子：
4.9
通讯作者：
Yamada, Shizuo
中科院分区：
文献类型：
--
作者：
Kawabata, Yohei;Aoki, Yosuke;Yamada, Shizuo
曲尼司特（TL）已被临床用于治疗气道炎症性疾病，但由于其溶解性差和全身副作用，其临床应用受到限制。为了克服这些缺点，使用TL的可吸入固体分散体（CSD/TL）开发了用于吸入治疗的新型TL可吸入粉末（CSD/TL-RP）。对CSD/TL-RP进行了稳定性研究，重点是吸入性能。即使在室温下储存6个月后，与储存前相比，载体颗粒表面上的微粉化颗粒也没有显著的形态变化。对CSD/TL-RP的级联撞击器分析表明，在排放剂量和细颗粒分数（FPF）约为100%的情况下，具有较高的吸入性能。98%和60%。CSD/TL-RP的长期储存仅导致FPF值略微降低（约10%）。54%）。吸入CSD/TL-RP可以减轻大鼠抗原诱导的炎症事件，表现为支气管肺泡灌洗液中的粒细胞和炎症生物标志物如嗜酸性粒细胞过氧化物酶、髓过氧化物酶和乳酸脱氢酶的显著减少。这些发现与核因子-κ B和环氧合酶-2（典型炎症介质）的mRNA表达水平降低一致。鉴于这些发现，TL吸入制剂可能是一种有趣的替代口服治疗哮喘和其他气道炎症性疾病的治疗具有足够的分散稳定性。(C)2010 Elsevier B. V.保留所有权利。
Tranilast (TL) has been clinically used for the treatment of airway inflammatory diseases, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). Stability study on CSD/TL-RP was carried out with a focus on inhalation performance. Even after 6 months of storage at room temperature, there were no significant morphological changes in micronized particles on the surface of carrier particles as compared with that before storage. Cascade impactor analyses on CSD/TL-RP demonstrated high inhalation performance with emitted dose and fine particle fraction (FPF) of ca. 98% and 60%, respectively. Long-term storage of CSD/TL-RP resulted in only a slight decrease in FPF value (ca. 54%). Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by marked reduction of granulocytes in bronchoalveolar lavage fluid and inflammatory biomarkers such as eosinophil peroxidase, myeloperoxidase, and lactate dehydrogenase. These findings were consistent with decreased expression levels of mRNAs for nuclear factor-kappa B and cyclooxygenase-2, typical inflammatory mediators. Given these findings, inhalable TL formulation might be an interesting alternative to oral therapy for the treatment of asthma and other airway inflammatory diseases with sufficient dispersing stability. (C) 2010 Elsevier B.V. All rights reserved.