Magnetic targeted delivery of dexamethasone acetate across the round window membrane in guinea pigs.
Magnetic targeted delivery of dexamethasone acetate across the round window membrane in guinea pigs.
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DOI：
10.1097/mao.0b013e318277a40e
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Dormer KJ
中科院分区：
文献类型：
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作者：
Du X;Chen K;Kuriyavar S;Kopke RD;Grady BP;Bourne DH;Li W;Dormer KJ
磁敏感的PLGA纳米颗粒将有效地靶向圆窗膜（RWM）以将醋酸地塞米松（Dex-Ac）递送至鼓阶。可以使用不同的靶向机制来实现治疗剂向特定组织的靶向递送。一种技术包括氧化铁纳米颗粒，易受外部磁场的影响。如果由生物相容性聚合物（PLGA）、磁铁矿和Dex-Ac组成的纳米复合材料可以被拉入并穿过哺乳动物RWM，则可以增强药物递送。首先使用RWM模型测量PLGA-磁铁矿-Dex-Ac纳米颗粒的体外靶向和释放动力学。接下来，这些优化的纳米复合材料通过填充麻醉豚鼠中的龛而靶向RWM。将永磁体放置在RWM对面1小时。在安乐死后收获臀部软组织、外淋巴液和RWM，并使用HPLC测量类固醇水平。膜运输，在体外，证明最佳的靶向使用较低的颗粒磁铁矿浓度（1与5或10毫克/毫升）。体内靶向PLGA-磁铁矿-Dex-Ac颗粒的平均尺寸为482.8 ± 158 nm（DLS），平均zeta电位为− 19.9 ± 3.3 mV。在1小时内，与单独扩散相比，Dex或Dex-Ac的耳蜗靶向递送显著增加。超顺磁性PLGA-磁铁矿-Dex-Ac纳米颗粒在外部磁场（0.26 mT）下1小时显著增加了Dex-Ac向内耳的递送。RWM没有完全渗透，并且也装载有纳米复合材料，这表明通过PLGA降解和被动扩散，向耳蜗的递送将持续数周。
Magnetically susceptible PLGA nanoparticles will effectively target the round window membrane (RWM) for delivery of dexamethasone-acetate (Dex-Ac) to the scala tympani. Targeted delivery of therapeutics to specific tissues can be accomplished using different targeting mechanisms. One technology includes iron oxide nanoparticles, susceptible to external magnetic fields. If a nanocomposite composed of biocompatible polymer (PLGA), magnetite, and Dex-Ac can be pulled into and across the mammalian RWM, drug delivery can be enhanced. In vitro targeting and release kinetics of PLGA-magnetite-Dex-Ac nanoparticles first were measured using a RWM model. Next, these optimized nanocomposites were targeted to the RWM by filling the niche in anesthetized guinea pigs. A permanent magnet was placed opposite the RWM for 1 hour. Cochlear soft tissues, perilymph, and RWM were harvested after euthanasia and steroid levels were measured using HPLC. Membrane transport, in vitro, proved optimal targeting using a lower particle magnetite concentration (1 versus 5 or 10 mg/ml). In vivo targeted PLGA-magnetite-Dex-Ac particles had an average size of 482.8 ± 158 nm (DLS) and an average zeta potential −19.9 ± 3.3 mV. In 1 hour, there was significantly increased cochlear targeted delivery of Dex or Dex-Ac, compared with diffusion alone. Superparamagnetic PLGA-magnetite-Dex-Ac nanoparticles under an external magnetic field (0.26 mT) for 1 hour significantly increased Dex-Ac delivery to the inner ear. The RWM was not completely permeated and also became loaded with nanocomposites, indicating that delivery to the cochlea would continue for weeks by PLGA degradation and passive diffusion.