Cai Hui, Wen Xingxing, Wen Lu, Tirelli Nicola, Zhang Xiao, Zhang Yue, Su Huanpeng, Yang Fan, Chen Gang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.
School of Materials, University of Manchester, Manchester, United Kingdom ; School of Biomedicine, University of Manchester, Manchester, United Kingdom.
Int J Nanomedicine. 2014 Dec 1;9:5591-601. doi: 10.2147/IJN.S72555. eCollection 2014.
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 AUC(0-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.
在本文中，通过向豚鼠圆窗（RW）给药不同的纳米颗粒（NPs），研究了聚（D，L-丙交酯-乙交酯酸）（PLGA）纳米颗粒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纳米颗粒中，以研究其穿过RWM的能力。然后，开发了负载丹酚酸B（Sal B）、丹参酮IIA（TS IIA）和三七总皂苷（PNS，包括人参皂苷R1（R1）、人参皂苷Rg1（Rg1）和人参皂苷Rb1（Rb1））的PLGA纳米颗粒，以评估负载复合药物的纳米颗粒是否会穿过RWM并提高这些药物的局部生物利用度。采用乳化溶剂蒸发法制备了负载单一或复合药物的PLGA纳米颗粒，并对其粒径分布、颗粒形态和包封率进行了表征。体外释放研究表明，纳米颗粒中Sal B、TS IIA和PNS具有缓释特性。药代动力学结果表明，应用于RWM的纳米颗粒显著改善了内耳内的药物分布。纳米颗粒经RW给药后，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，应用纳米颗粒后R1、Rg1和Rb1的AUC(0-t)分别高4.0、3.1和7.1倍，Cmax分别高14.4、10.0和16.7倍。这些发现表明，在纳米尺度具有独特性质的PLGA纳米颗粒具有强大的能力，可通过RWM将单一或复合药物转运至PL中，并显著提高内耳中包封药物的局部生物利用度。使用PLGA纳米颗粒作为纳米级递送载体携带药物穿过RWM可能是治疗内耳疾病的一种有前景的策略。
