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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。
Objective To study the transport pathway of fluorescent probe after administration in the inner ear. METHODS: Coumarin-6 was used as a fluorescent probe to prepare lactic acid / glycolic acid copolymer (PLGA) nanoparticles by emulsion-solvent evaporation method. The nanoparticles and solution were introduced into the inner ear of guinea pig through unilateral tympanic injection. At the time point, drug-induced perilymph (PL), contralateral PL, cerebrospinal fluid (CSF) and plasma were collected. The concentration of coumarin-6 in each tissue was determined by HPLC and the pharmacokinetic parameters were calculated. Results Coumarin-6 was distributed in PL, contralateral PL and CSF in unilateral tympanic cavity after injection of nanoparticles and solution. Compared with the solution, the AUC of Coumarin-6 on the administration side of PL and CSF increased by 3.7 and 7.6 times, respectively, and the ρmax increased by 9.9 and 9.0 times, respectively, and MRT prolonged by 5.1 and 9.4 times respectively. CONCLUSIONS: The administration route of inner ear administration is PL → CSF → contralateral PL on the administration side, and administration of nanoparticles can significantly improve the local bioavailability of inner ear and CSF and prolong the action time.