目的 采用皮肤、血液双位点同步微透析技术研究雷公藤甲素普通凝胶、纳米乳、纳米乳凝胶在大鼠皮肤和血液中的药动学过程。方法 微透析系统包括皮肤线性探针和血管同心圆探针,分别用来测定雷公藤甲素在皮肤、血液中的回收率。SD大鼠腹部脱毛后植入皮肤探针、血管同心圆探针。以空白PBS为灌流液,平衡1 h 后各组动物腹部分别给予雷公藤甲素普通凝胶、雷公藤甲素纳米乳和雷公藤甲素纳米乳凝胶。每隔30 min收集1次透析液,连续收集12 h。采用LC-MS测定透析液中雷公藤甲素的含量。结果 雷公藤甲素纳米乳和纳米乳凝胶皮肤和血液的AUC0-t明显高于雷公藤甲素普通凝胶,且雷公藤甲素纳米乳凝胶缓释效果更加明显,显著提高了雷公藤甲素的生物利用度。结论 皮肤、血液双位点同步微透析技术能够检测大鼠皮肤及血液内药物浓度,为雷公藤甲素的药动学研究提供了新方法。
Abstract
OBJECTIVE To investigate the pharmacokinetics of triptolide gels, nanoemulsions and nanoemulsion gels by simultaneous skin and blood microdialysis in rats. METHODS The microdialysis systems include linear probes and vascular probes which are used for measuring the recovery of triptolide in skin and blood, respectively. Linear probe and vascular probe were implanted in SD rats after abdominal hair removal. Triptolide gels, nanoemulsions and nanoemulsion gels were administered to SD rats. The probe was continuously perfused with PBS(pH 7.4) at a flow rate of 3 μL·min-1. Dialysate samples were collected every 30 min and continuously performed for 12 h. The dialysis samples were determined by LC-MS. RESULTS The AUC0-t(s) of triptolide nanoemulsions and nanoemulsion gels were significantly higher than those of triptolide gels in skin and blood. Moreover, compared with the concentration of triptolide nanoemulsions in skin and blood, triptolide was released more smoothly from nanoemulsion gels, providing a sustained release effect and an improved bioavailability. CONCLUSION The technique of simultaneous skin and blood microdialysis is able to detect the concentration of drug in the skin and blood of rats, which provides a new method for the pharmacokinetic study of tripolide.
关键词
雷公藤甲素 /
纳米乳 /
纳米乳凝胶 /
微透析 /
经皮给药 /
药动学
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Key words
tripolide /
nanoemulsion /
nanoemulsion gel /
microdialysis /
transdermal delivery system /
pharmacokinetics
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中图分类号：
R944
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参考文献
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脚注
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基金
国家自然科学基金项目资助(81573613, 81373896);天然药物活性组分与药效国家重点实验室开放课题(SKLNMKF201809); 上海市人才发展基金项目资助(201658)
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