基于荧光探针内耳给药转运通路的考察

陈钢 张晓 牧磊 邵阿丽 李晓芳 王伟菊

中国药学杂志 ›› 2012, Vol. 47 ›› Issue (4) : 279-282.

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中国药学杂志 ›› 2012, Vol. 47 ›› Issue (4) : 279-282.
论著

基于荧光探针内耳给药转运通路的考察

  • 陈钢1, 2,张晓1,牧磊1,邵阿丽1,李晓芳1,王伟菊1
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Transport Route of Fluorescent Probe via Inner Ear Administration

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摘要

目的 研究荧光探针经内耳给药后的转运通路。方法 以香豆素-6为荧光探针,采用乳化-溶剂挥发法制备乳酸/羟基乙酸共聚物(PLGA)纳米粒,经单侧鼓室注射分别将其纳米粒及溶液剂导入豚鼠内耳,于不同时间点采集给药侧外淋巴液(PL)、对侧PL、脑脊液(CSF)和血浆,采用 HPLC测定各组织中香豆素-6的浓度,并计算药动学参数。结果 单侧鼓室注射纳米粒及溶液剂后,香豆素-6在给药侧PL、对侧PL及CSF中均有分布。与溶液剂相比,鼓室注射纳米粒后,香豆素-6在给药侧PL和CSF的AUC分别增加3.7、7.6倍,ρmax分别提高9.9、9.0倍,而且MRT 分别延长5.1、9.4倍。结论 内耳给药的转运途径为给药侧PL→CSF→对侧PL,并且采用纳米粒给药能显著提高内耳及CSF的局部生物利用度,延长作用时间。

Abstract

OBJECTIVE To investigate transport route of fluorescent probe following inner ear administration. METHODS Coumarin-6 (CM) was employed as fluorescent probe and CM-loaded poly(lactic-co-glycolic acid) nanoparticles (CM-PLGA-NP) were prepared by emulsification-solvent evaporation method. Perilymph (PL), contralateral PL, cerebrospinal fluid (CSF) and plasma were collected periodically in guinea pigs after unilateral intratympanic administration of CM-PLGA-NP or CM solution. The concentrations of CM were determined by high performance liquid chromatography (HPLC), and statistic program DAS was applied to the calculation of pharmacokinetic parameters. RESULTS CM was found in PL, contralateral PL and CSF after unilateral intratympanic administration of CM-PLGA-NP or CM solution. The AUC in PL and CSF following intratympanic administration of CM-PLGA-NP were respectively 3.7 and 7.6-fold higher than those following intratympanic administration of CM solution. And the ρmax in PL and CSF were respectively 9.9 and 9.0-fold higher. Moreover, CM-PLGA-NP extended the MRT in PL and CSF by 5.1 and 9.4 times compared with CM solution. CONCLUSION Transport pathway of intra-cochlear administration is PL→CSF→contralateral PL. Nanoparticles can greatly improve drug distribution within the inner ear and CSF, and prolong the residence time.

关键词

香豆素-6 / 内耳给药 / 转运途径 / PLGA纳米粒

Key words

coumarin-6 / intra-cochlear administration / transport route / PLGA nanoparticle

引用本文

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陈钢 张晓 牧磊 邵阿丽 李晓芳 王伟菊 . 基于荧光探针内耳给药转运通路的考察[J]. 中国药学杂志, 2012, 47(4): 279-282
Transport Route of Fluorescent Probe via Inner Ear Administration[J]. Chinese Pharmaceutical Journal, 2012, 47(4): 279-282

参考文献


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基金

国家自然科学基金资助项目(30801553);广东药学院师资队伍建设经费资助
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