Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration.
Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration.
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通过圆窗给药应用 PLGA 纳米粒子，增强单一或复合药物递送至内耳的局部生物利用度
DOI：
10.2147/ijn.s72555
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发表时间：
2014
影响因子：
8
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Cai H;Wen X;Wen L;Tirelli N;Zhang X;Zhang Y;Su H;Yang F;Chen G
在本文中，在给豚鼠圆窗（RW）施用不同的纳米粒子（RW）后，检查了聚（d，l-丙交酯-乙交酯酸）（PLGA）纳米粒子（NP）携带单一或复合药物穿过圆窗膜（RWM）的潜力。首先，将香豆素 6 作为荧光探针掺入 PLGA NP，以研究其穿过 RWM 的能力。然后，开发了含有丹酚酸B（Sal B）、丹参酮IIA（TS IIA）和总三七皂苷（PNS）（包括三七皂苷R1（R1）、人参皂苷Rg1（Rg1）和人参皂苷Rb1（Rb1））的PLGA NP，以评估负载复合药物的NP是否可以通过RWM并提高这些药物的局部生物利用度代理。采用乳化溶剂蒸发法制备负载单一或复合药物的PLGA纳米粒，并对其粒径分布、颗粒形貌和包封率进行表征。体外释放研究显示了 NP 中 Sal B、TS IIA 和 PNS 的缓释特性。药代动力学结果表明，应用于 RWM 的 NP 显着改善了内耳内的药物分布。 RW 施用 NP 后外淋巴 (PL) 中香豆素 6 的 AUC0–t 比香豆素 6 溶液高 4.7 倍，Cmax 高 10.9 倍。此外，与复合溶液相比，应用纳米粒子后，R1、Rg1 和 Rb1 的 AUC0-t 分别高出 4.0、3.1 和 7.1 倍，Cmax 分别高出 14.4、10.0 和 16.7 倍。这些发现表明，在纳米级尺寸上具有独特性质的PLGA NP具有强大的能力，可以通过RWM将单一或复合药物转运到PL中，并显着增强内耳中封装药物的局部生物利用度。使用 PLGA NP 作为纳米级递送载体来携带药物穿过 RWM 可能是治疗内耳疾病的一种有前途的策略。
In this paper, the potential of poly(d,l-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) for carrying single or compound drugs traversing the round window membrane (RWM) was examined after the round window (RW) administration of different NPs to guinea pigs. First, coumarin-6 was incorporated into PLGA NPs as a fluorescent probe to investigate its ability to cross the RWM. Then, PLGA NPs with salvianolic acid B (Sal B), tanshinone IIA (TS IIA), and total panax notoginsenoside (PNS) including notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Rb1 (Rb1) were developed to evaluate whether NPs loaded with compound drugs would pass through the RWM and improve the local bioavailability of these agents. PLGA NPs loaded with single or compound drugs were prepared by the emulsification solvent evaporation method, and their particle size distribution, particle morphology, and encapsulation efficiency were characterized. In vitro release study showed sustained-release profiles of Sal B, TS IIA, and PNS from the NPs. The pharmacokinetic results showed that NPs applied to the RWM significantly improved drug distribution within the inner ear. The AUC0–t of coumarin-6 in the perilymph (PL) following RW administration of NPs was 4.7-fold higher than that of coumarin-6 solution, and the Cmax was 10.9-fold higher. Furthermore, the AUC0–t of R1, Rg1, and Rb1 were 4.0-, 3.1-, and 7.1-fold greater, respectively, after the application of NPs compared to the compound solution, and the Cmax were, respectively, 14.4-, 10.0-, and 16.7-fold higher. These findings suggest that PLGA NPs with unique properties at the nanoscale dimensions have a powerful ability to transport single or compound drugs into the PL through the RWM and remarkably enhance the local bioavailability of the encapsulated drugs in the inner ear. The use of PLGA NPs as nanoscale delivery vehicles to carry drugs across the RWM may be a promising strategy for the treatment of inner ear diseases.