Transport route of fluorescent probe via inner ear administration / 中国药学杂志

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. Copyright 2012 by the Chinese Pharmaceutical Association.