摘要
本文探寻经内耳途径输送药物到脑部的可行性,为脑靶向给药提供一条崭新的研究思路。制备醋酸地塞米松(DA)固体脂质纳米粒(SLN),建立相应的HPLC含量测定方法。经静脉和鼓室注射DA-SLN,并与地塞米松磷酸钠(DSP)溶液相比较,测定药物在脑脊液(CSF)和内耳外淋巴液(PL)中的浓度及药代动力学参数。结果表明,与静脉注射比较,鼓室注射药物在CSF的局部生物利用度显著提高,鼓室注射DA-SLN比静脉注射高2.5倍,鼓室注射DSP溶液比静脉注射高4.3倍。与DSP溶液比较,鼓室注射DA-SLN能明显增加进入CSF的药量和延长药物的作用时间,AUC和MRT分别较前者高13和19倍;并且药物在PL中分布减少,其AUC低76%。提示经内耳途径给药有望成为一种新的脑靶向方法,值得进一步研究。
The article investigates the feasibility of delivering drugs to brain via inner ear, and provides a novel route for delivering drugs to the brain tissues. Dexamethasone acetate （ DA）-loaded solid lipid nanoparticles （SLN） was prepared by using Compritol 888 ATO as material. HPLC assays for the determination of DA, dexamethasone sodium phosphate （DSP） and dexamethasone （Dex） were developed, separately. DA-loaded SLN and DSP solution were administered after intratympanic injection （IT） or intravenous injection （IV）. Perilymph （PL） and cerebrospinal fluid （CSF） were collected periodically. The concentrations in PL and CSF were measured by HPLC, and used to estimate pharmacokinetic parameters of Dex in CSF. The AUC of Dex in CSF following IT DA-loaded SLN or DSP solution were respectively 2.5 and 4.3-fold higher than those following IV. After IT, DA-loaded SLN increased the AUC by 13 times and extended the MRT by 19 times, compared with the solution. Moreover, the AUC of Dex in PL following IT the SLN was 76% lower than that following IT the solution. Intra-cochlear administration shows great potential and offers a promising alternative to brain-targeted drug delivery.
出处
《药学学报》
CAS
CSCD
北大核心
2007年第10期1102-1106,共5页
Acta Pharmaceutica Sinica
基金
广东省自然科学基金资助项目(7301575).
关键词
脑靶向给药
鼓室给药
地塞米松
固体脂质纳米粒
外淋巴
brain-targeted drug delivery
intratympanic administration
dexamethasone
solid lipid nanoparticle
perilymph
