Round window membrane intracochlear drug delivery enhanced by induced advection.
Round window membrane intracochlear drug delivery enhanced by induced advection.
复制标题
DOI：
10.1016/j.jconrel.2013.11.021
复制
发表时间：
2014-01-28
期刊：
影响因子：
--
通讯作者：
Frisina RD
中科院分区：
文献类型：
--
作者：
Borkholder DA;Zhu X;Frisina RD
经由通过圆窗膜（RWM）吸收将治疗性化合物递送至内耳具有优于直接耳蜗内输注的优点;具体地，最小化对功能性听力测量的影响。然而，先前的报告显示，发生显著的基底-顶端浓度梯度，可能影响治疗效果。在这里，我们提出了一种新的方法，内耳药物输送与诱导平流帮助分布的化合物在整个内耳在小鼠耳蜗。将聚酰亚胺微管放置在RWM龛附近，通过水泡造口术进入中耳腔，允许将化合物直接递送至RWM。我们假设后半规管造口会由于脑脊液的流入而引起从开放的耳蜗导水管到管造口的顶流。为了验证这一假设，将年轻的成年CBA/CaJ小鼠分为两组：仅采用膀胱造口法（BA）和膀胱造口+小管造口法（B+C）。应用畸变产物耳声发射（DPOAE）和听性脑干反应（ABR）阈值，在中耳灌注水杨酸人工外淋巴液（AP）期间和之后，应用于RWM附近。小鼠恢复1周，并重新测试。结果表明，使用RWM手术（有或没有泪小管造口术）对听觉功能没有显著影响，并且在水杨酸盐输注期间DPOAE阈值可逆性升高。比较两种方法的阈值偏移，B+C方法比BA方法具有更多的生理效应，包括在代表更顶端耳蜗位置的较低频率下。与小鼠耳蜗造口不同，手术后1周恢复后没有有害的听觉功能影响。B+C方法在较低频率下具有更多的药物功效，强调了更精确控制内耳治疗化合物递送的潜在益处。
Delivery of therapeutic compounds to the inner ear via absorption through the round window membrane (RWM) has advantages over direct intracochlear infusions; specifically, minimizing impact upon functional hearing measures. However, previous reports show that significant basal-to-apical concentration gradients occur, with the potential to impact treatment efficacy. Here we present a new approach to inner ear drug delivery with induced advection aiding distribution of compounds throughout the inner ear in the murine cochlea. Polyimide microtubing was placed near the RWM niche through a bullaostomy into the middle ear cavity allowing directed delivery of compounds to the RWM. We hypothesized that a posterior semicircular canalostomy would induce apical flow from the patent cochlear aqueduct to the canalostomy due to influx of cerebral spinal fluid. To test this hypothesis, young adult CBA/CaJ mice were divided into two groups: bullaostomy approach only (BA) and bullaostomy + canalostomy (B+C). Cochlear function was evaluated by distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) thresholds during and after middle ear infusion of salicylate in artificial perilymph (AP), applied near the RWM. The mice recovered for 1 week, and were re-tested. The results demonstrate there was no significant impact on auditory function utilizing the RWM surgical procedure with or without the canalostomy, and DPOAE thresholds were elevated reversibly during the salicylate infusion. Comparing the threshold shifts for both methods, the B+C approach had more of a physiological effect than the BA approach, including at lower frequencies representing more apical cochlear locations. Unlike mouse cochleostomies, there was no deleterious auditory functional impact after 1 week recovery from surgery. The B+C approach had more drug efficacy at lower frequencies, underscoring potential benefits for more precise control of delivery of inner ear therapeutic compounds.
登录
查看更多内容
影响因子：
2.8
作者：
Salt, AN;Ma, YL
通讯作者：
Ma, YL
影响因子：
2.8
作者：
Cederholm, Jennie M. E.;Froud, Kristina E.;Wong, Ann C. Y.;Ko, Myungseo;Ryan, Allen F.;Housley, Gary D.
通讯作者：
Housley, Gary D.
影响因子：
12.4
作者：
Kawamoto, K;Oh, SH;Raphael, Y
通讯作者：
Raphael, Y
DOI：
10.1097/00020840-200310000-00005
发表时间：
2003-10-01
影响因子：
1.6
作者：
Hoffmann, Karen K;Silverstein, Herbert
通讯作者：
Silverstein, Herbert
DOI：
10.1523/jneurosci.3852-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Puligilla C;Dabdoub A;Brenowitz SD;Kelley MW
通讯作者：
Kelley MW