title: A novel aerosol-mediated drug delivery system for inner ear therapy: intratympanic aerosol methylprednisolone can attenuate acoustic trauma.
abstract: We developed a novel aerosol-mediated drug delivery system for inner ear therapy by using a silicon-based multiple-Fourier horn nozzle. Intratympanic aerosol (ITA) methylprednisolone (MP) delivery can protect hearing after acoustic trauma. The highest concentration of MP (38.9 ± 5.47 ppm) appeared at 2 h and declined rapidly within 10 h. The concentrations of MP remained at a relatively low level for more than 10 h. Compared to the baseline, the auditory brainstem response (ABR) thresholds shifted markedly at 1 h after noise exposure in all groups (p < 0.05). From the cochleograms, it can be noted that the main lesions encompassed the 2-20 kHz frequency range. Significant differences ( ) were observed for the range between 5 and 8 kHz in the cell loss of outer hair cells (OHCs). The losses for IHCs were lower than for OHCs. The MP movement in the middle ear was simulated by a convection diffusion equation with a relaxation time. The relaxation time was 0.5 h, and the concentration threshold of MP on the round window membrane (RWM) in the middle ear (C T) was 8900 ppm. Using the unit hydrograph (UH) method, we obtained a proper boundary concentration on the RWM at the cochlea, which resulted in a well-fit concentration. Finally, a linking mechanism between the middle ear and the cochlea was established by the RWM. The adjustable permeability and concentration threshold provide the flexibility to match the peak times and peak values of the concentration on the RWM in the middle ear and the cochlea.
authors.affiliation: National Center for High-Performance Computing and National Applied Research laboratories, Hsinchu 30076, Taiwan. c00lml00@nchc.narl.org.tw
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Li
authors.forename: Lung-Cheng
authors.initials: LC
authors.lastname: Lee
authors.forename: Yuh-Ren
authors.initials: YR
authors.lastname: Cheng
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Yuan-Fang
authors.initials: YF
authors.lastname: Chou
authors.forename: Yuh-Shyang
authors.initials: YS
authors.lastname: Chen
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Yao
authors.forename: Peir-Rong
authors.initials: PR
authors.lastname: Chen
authors.forename: Chuan-Jen
authors.initials: CJ
authors.lastname: Hsu
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Song
authors.forename: Chia-Fone
authors.initials: CF
authors.lastname: Lee
mesh_terms: D000336:Aerosols / Q000008:administration & dosage / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000818:Animals; D003051:Cochlea / Q000737:chemistry / Q000187:drug effects* / Q000293:injuries*; D016503:Drug Delivery Systems / Q000379:methods*; D004432:Ear, Middle; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008954:Models, Biological; D010498:Perilymph / Q000737:chemistry; D010539:Permeability; D012405:Round Window, Ear / Q000378:metabolism; D014432:Tympanic Membrane / Q000502:physiology
chemical_list: D000336:Aerosols; D008775:Methylprednisolone