title: [Preliminary study on brain-targeted drug delivery via inner ear].
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Shi-xiang
authors.initials: SX
authors.lastname: Hou
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.forename: Miao-zhen
authors.initials: MZ
authors.lastname: Jin
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D007758:Ear, Inner / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry; D005260:Female; D006168:Guinea Pigs; D054709:Lecithins; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D010498:Perilymph / Q000378:metabolism; D011897:Random Allocation; D013501:Surface-Active Agents / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D054709:Lecithins; D013501:Surface-Active Agents; C086409:glyceryl behenate; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; C018038:dexamethasone acetate