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| 凝集素化昔萘酸沙美特罗纳米粒-微粒的药效和药动学研究 |
| 李慧1,2,董文凤1,2,杜丽2,董新威3,谢敏强3,李凤前2* |
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(1. 江苏大学药学院药剂学教研室,镇江 212013
2. 上海市第八人民医院药剂科,上海 200235
3. 浙江大学医学院国家食品药品监督管理局浙江呼吸药物研究实验室,杭州 310058
*通信作者) |
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| 摘要: |
| 目的 研究小鼠体内干粉吸入麦胚凝集素(WGA)化修饰的昔萘酸沙美特罗(SalX)纳米粒-微粒(NiMS)的药效学及药动学。方法 通过皮下和腹腔注射卵清蛋白(OVA)建立小鼠肺哮喘病理模型,经气道干粉吸入给予WGA-SalX-NiMS粉末,采用对照实验法,检测给药后的肺组织及气道炎症情况,并对药物在小鼠血浆和肺组织中的药代动力学行为进行研究。数据用Sigma State统计软件包处理。结果 与模型组相比,SalX-NiMS组和WGA-SalX-NiMS组小鼠支气管肺泡灌洗液(BALF)中白细胞总数、嗜酸粒细胞、淋巴细胞及巨噬细胞数目呈下降趋势。WGA-SalX-NiMS组小鼠BALF中淋巴细胞及巨噬细胞数与SalX-NiMS组相比减少(P<0.05)。在小鼠血浆中,SalX-NiMS组的tmax为1.500 h,Cmax为57.366 mg/L,t1/2β为69.315 h,AUC0-∞为2 427.205 mg·L-1·h,MRT0-∞为55.294 h；WGA-SalX-NiMS组的tmax为1.000 h,Cmax为62.581 mg/L,t1/2β为69.315 h,AUC0-∞为4 071.838 mg·L-1·h,MRT0-∞为75.094 h。在小鼠肺组织中,SalX-NiMS组的tmax为0.083 h,Cmax为0.497 μg/mg,t1/2β为11.231 h,AUC0-∞为3.936 μg·mg-1·h,MRT 0-∞为13.854 h；WGA-SalX-NiMS组的tmax为0.083 h,Cmax为0.796 μg/mg,t1/2β为27.294 h,AUC0-∞为5.578 μg·mg-1·h,MRT0-∞为26.330 h。WGA-SalX-NiMS组的血浆及肺组织药物浓度均高于SalX-NiMS组(P<0.05)。结论 WGA修饰后的SalX-NiMS在小鼠体内易于释药,血浆和肺组织中药物浓度较高,有利于哮喘发作时炎症的控制与改善。 |
| 关键词: 昔萘酸沙美特罗 纳米粒-微粒系统 麦胚凝集素 药物效应动力学 药代动力学 |
| DOI： |
| 投稿时间：2013-05-07修订日期：2013-06-24 |
| 基金项目:国家自然科学基金(30973661, 81172989). |
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| Nanoparticles-in-microparticles loaded with lectin-anchored salmeterol xinafoate: a pharmacodynamics and pharmacokinetics study |
| LI Hui1,2,DONG Wen feng1,2,DU Li2,DONG Xin wei3,XIE Min qiang3,LI Feng qian2* |
(1. Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, Jiangsu, China
2. Department of Pharmacy, Shanghai Eighth People’s Hospital, Shanghai 200235, China
3. Zhejiang Respiratory Drug Research Laboratory of State Food and Drug Administration, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China
*Corresponding author.) |
| Abstract: |
| Objective To study the pharmacodynamics and pharmacokinetics of inhaled dry powder of nanoparticles-in-microparticles system (NiMS) loaded with wheat germ agglutinin (WGA)-anchored salmeterol xinafoate (SalX) in mice. Methods The asthma model was established by subcutaneous and intraperitoneal injection of ovalbumin (OVA) in mice. WGA-SalX-NiMS powder was delivered to mice through airway dry powder inhalation. Reference method was applied in this study. The lung tissue and airway inflammation were examined, and the pharmacokinetics of SalX in the plasma and lung tissue of mice were studied after the administration of WGA-SalX-NiMS. The concentration-time data was analyzed using Sigma State statistical package. Results Compared with the model group, the counts of white cells, eosinophils, lymphocytes and macrophages in the bronchoalveolar lavage fluid (BALF) of mice in SalX-NiMS group and WGA-SalX-NiMS group showed a descending trend. The BALF counts of lymphocytes and macrophages in WGA-SalX-NiMS group were significantly less than those in SalX-NiMS group (P<0.05). The plasma pharmacokinetics parameters of mice were as follows: tmax 1.500 h, Cmax 57.366 mg/L, t1/2β 69.315 h, AUC0-∞ 2 427.205 mg·L-1·h, MRT0-∞ 55.294 h for SalX-NiMS; tmax 1.000 h, Cmax 62.581 mg/L, t1/2β 69.315 h, AUC0-∞ 4 071.838 mg·L-1·h, MRT0-∞ 75.094 h for WGA-SalX-NiMS. The pharmacokinetics parameters of lung tissue of mice were as follows: tmax 0.083 h, Cmax 0.497 μg/mg, t1/2β 11.231 h, AUC0-∞ 3.936 μg·mg-1·h, MRT0-∞ 13.854 h for SalX-NiMS; tmax 0.083 h, Cmax 0.796 μg/mg, t1/2β 27.294 h, AUC0-∞ 5.578 μg·mg-1·h, MRT0-∞ 26.330 h for WGA-SalX-NiMS. The drug concentrations of WGA-SalX-NiMS in both plasma and lung tissue were significantly higher than those of SalX-NiMS (P<0.05). Conclusion The drug release rate of SalX-NiMS is promoted and the drug concentrations in the plasma and lung tissue are increased after the modification with WGA, which contributes to the control and improvement of the airway inflammation during asthmatic attack. |
| Key words: salmeterol xinafoate nanoparticles-in-microparticles system wheat germ agglutinin pharmacodynamics pharmacokinetics |
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