Novel ultra-small micelles based on rebaudioside A: A potential nanoplatform for ocular drug delivery
Novel ultra-small micelles based on rebaudioside A: A potential nanoplatform for ocular drug delivery
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基于莱鲍迪甙 A 的新型超小胶束：眼部药物输送的潜在纳米平台
DOI：
10.1016/j.ijpharm.2018.10.006
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发表时间：
2018
影响因子：
5.8
通讯作者：
Xianggen Wu
中科院分区：
文献类型：
--
作者：
Kaichao Song;Meng Xin;Hongxia Yu;Zhou Zheng;Jun Li;Mengshuang Li;Huimin Guo;Youlan Tan;Xianggen Wu
我们研究了莱鲍迪苷A（RA）的自组装胶束是否可以作为眼部给药系统。RA自组装成粒径小于4 nm的胶束，且分散性指数小于0.3，呈均匀分布。RA具有良好的细胞耐受性，在浓度≤ 18.5mg/ml时，孵育72 h未观察到细胞毒性。RA浓度≤ 12 mg/ml时也不引起细胞凋亡。香豆素-6（Cou 6）载药的RA胶束具有良好的细胞耐受性和体内对兔眼无刺激性。RA胶束显著提高了细胞对Cou 6的摄取（与游离Cou 6相比P < 0.05）;在离体角膜内吞机制测试中，明显涉及能量不依赖的、活跃的细胞内吞途径，并且观察到细胞器如溶酶体、内质网和线粒体具有高分布的Cou 6，而更复杂的内吞途径明显涉及。与游离Cou 6滴眼液相比，RA胶束的使用显著提高了包封Cou 6滴眼液的体外角膜渗透性（P< 0.05）。这些结果表明，RA胶束制剂作为一种新型的眼部给药系统，以提高疏水性药物的生物利用度有很大的潜力。
We investigated if the self-assembled micelles of rebaudioside A (RA) could potentially be utilized as an ocular drug-delivery system in this investigation. RA self-assembled into micelles with ultra-small particle sizes (<4 nm) in a homogeneous distribution state (polydispersity index < 0.3). RA had good cellular tolerance and no cytotoxicity was observed at concentrations ≤ 18.5 mg/ml at 72 h of incubation. RA also did not cause cell apoptosis at concentration ≤ 12 mg/ml. Coumarin-6 (Cou6)-loaded RA micelles had good cellular tolerance andin vivonon-irritants to the rabbit eyes. RA micelles dramatically improved the cellular uptake of Cou6 (compared to free-Cou6P< 0.05); an energy-independent, active, intracellular endocytosis pathway was apparently involved, and cellular organelles such as lysosomes, endoplasmic reticuli, and mitochondria were observed with a high distribution of Cou6, while a much more sophisticated endocytosis pathway was apparently involved in theex vivocorneal endocytosis mechanism tests. The use of RA micelles significantly improvedin vivocorneal permeation of the encapsulated Cou6 when compared to free-Cou6 eye drops (P< 0.05). These findings indicate that RA micelle formulations have great potential as a novel ocular drug-delivery system to improve the bioavailability of hydrophobic drugs.