Persistence, distribution, and impact of distinctly segmented microparticles on cochlear health following in vivo infusion.
Persistence, distribution, and impact of distinctly segmented microparticles on cochlear health following in vivo infusion.
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体内输注后明显分段的微粒的持久性、分布和对耳蜗健康的影响。
DOI：
10.1002/jbm.a.35675
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Altschuler,RichardA
中科院分区：
文献类型：
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作者：
Ross,AstinM;Rahmani,Sahar;Prieskorn,DianeM;Dishman,AcaciaF;Miller,JosefM;Lahann,Joerg;Altschuler,RichardA
将药物递送到听觉功能障碍患者的耳蜗可能具有许多益处，从增强听神经存活到保护剩余的感觉细胞及其神经元连接。治疗需要平台，使药物能够直接输送到耳蜗，并提高干预的潜在功效。耳后植入物接受者是一个特定的患者亚组，可以从局部药物输送中受益，因为更多的候选人具有残余听力;由于残余听力直接影响植入后听力结果，因此需要保护植入物插入引起的创伤。本研究评估了利用微粒将药物递送到耳蜗液中的可行性，测试了持久性、分布、生物相容性和药物释放特性。为了允许递送多种治疗剂，颗粒由两个不同的隔室组成;一个含有聚丙交酯-共-乙交酯（PLGA），另一个由缩醛改性的葡聚糖和PLGA组成。体内输注后，图像分析显示微粒在耳蜗中持续存在至少7天，主要是在第一和第二圈。与输注前基线相比，大多数受试者在输注后7天的听性脑干反应阈值保持或仅轻微升高。耳蜗毛细胞仅有轻微至有限的损失，基于CD 45+免疫抑制的免疫应答可忽略不计。当输注载吡贝地尔微粒时，在输注后7天可在耳蜗液中检测到吡贝地尔。这些结果表明，分段微粒是相对惰性的，可以持久，释放其内容物，并在功能和生物学上与耳蜗功能相容，因此是有前途的车辆耳蜗药物输送。© 2016 Wiley Periodicals，Inc. J Biomed Mater Res Part A：104A：1510-1522，2016.
Delivery of pharmaceuticals to the cochleae of patients with auditory dysfunction could potentially have many benefits from enhancing auditory nerve survival to protecting remaining sensory cells and their neuronal connections. Treatment would require platforms to enable drug delivery directly to the cochlea and increase the potential efficacy of intervention. Cochlear implant recipients are a specific patient subset that could benefit from local drug delivery as more candidates have residual hearing; and since residual hearing directly contributes to post‐implantation hearing outcomes, it requires protection from implant insertion‐induced trauma. This study assessed the feasibility of utilizing microparticles for drug delivery into cochlear fluids, testing persistence, distribution, biocompatibility, and drug release characteristics. To allow for delivery of multiple therapeutics, particles were composed of two distinct compartments; one containing polylactide‐co‐glycolide (PLGA), and one composed of acetal‐modified dextran and PLGA. Followingin vivoinfusion, image analysis revealed microparticle persistence in the cochlea for at least 7 days post‐infusion, primarily in the first and second turns. The majority of subjects maintained or had only slight elevation in auditory brainstem response thresholds at 7 days post‐infusion compared to pre‐infusion baselines. There was only minor to limited loss of cochlear hair cells and negligible immune response based on CD45+ immunolabling. When Piribedil‐loaded microparticles were infused, Piribedil was detectable within the cochlear fluids at 7 days post‐infusion. These results indicate that segmented microparticles are relatively inert, can persist, release their contents, and be functionally and biologically compatible with cochlear function and therefore are promising vehicles for cochlear drug delivery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1510–1522, 2016.