Li Mengshuang, Xin Meng, Song Kaichao, Sun Fengyuan, Hou Yuzhen, Li Jun, Wu Xianggen
a Department of Pharmacy , College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao China.
b Pharmacy Intravenous Admixture Services , Qingdao Women and Children's Hospital , Qingdao , China.
Curr Eye Res. 2018 Mar;43(3):406-414. doi: 10.1080/02713683.2017.1401644. Epub 2017 Nov 16.
Purpose How to deliver enough medical agents to the trigeminal ganglion (TG) neurons conveniently still remains a challenge in pharmaceutics and clinics. The purpose of this study was to reveal that intranasal administration of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG) nanomicelle formulation could efficiently deliver agent to TG neurons in mice. Methods Ocular topical or intranasal administration of nanomicelle coumarin-6 was performed in mice, and tissue distribution after administration (0.25, 1, 2, 4, 6, 8, and 10 h) was analyzed. Fluoro-Gold was used as a retrograde tracer to identify corneal and nasal neurons in the TG. Pharmacokinetic profiles after ocular topical or intranasal administration were explored in detail. Results Coumarin-6 levels in the TG neurons were significantly higher in intranasal administration groups than in topical administration groups, and the difference was statistically significant (P < 0.05) at all time points except for 10 h. Interestingly, in cornea, coumarin-6 was detected after intranasal administration. For intranasal administration groups, it was also interestingly found that coumarin-6 levels in the TG neurons were much higher than that in the brain, suggesting that the TG neurons was a target tissue after the intranasal administration of nanomicelle coumarin-6. These levels also indicated the safety of brain tissue after intranasal administration. Using Fluoro-Gold tract tracing techniques, coumarin-6 was detected in TG neurons after either ocular topical or intranasal administration of nanomicelle coumarin-6, indicating the high colocalization of corneal and nasal neurons in the TG. Conclusions Intranasal administration of PVCL-PVA-PEG nanomicelle formulation could efficiently deliver to TG neurons, and it might be a promising therapy for pathological TG neurons.
目的 在制药学和临床实践中，如何将足够的药物制剂方便地递送至三叉神经节（TG）神经元仍然是一项挑战。本研究的目的是揭示经鼻给予聚乙烯己内酰胺 - 聚醋酸乙烯酯 - 聚乙二醇接枝共聚物（PVCL - PVA - PEG）纳米胶束制剂能够有效地将药物递送至小鼠的TG神经元。方法 对小鼠进行纳米胶束香豆素 - 6的眼部局部给药或经鼻给药，并分析给药后（0.25、1、2、4、6、8和10小时）的组织分布。使用荧光金作为逆行示踪剂来识别TG中的角膜和鼻神经元。详细探究眼部局部给药或经鼻给药后的药代动力学特征。结果 经鼻给药组TG神经元中的香豆素 - 6水平显著高于局部给药组，除10小时外，在所有时间点差异均具有统计学意义（P < 0.05）。有趣的是，在经鼻给药后在角膜中检测到了香豆素 - 6。对于经鼻给药组，还有趣地发现TG神经元中的香豆素 - 6水平远高于脑中的水平，这表明经鼻给予纳米胶束香豆素 - 6后TG神经元是靶组织。这些水平也表明了经鼻给药后脑组织的安全性。使用荧光金示踪技术，在纳米胶束香豆素 - 6眼部局部给药或经鼻给药后，在TG神经元中均检测到了香豆素 - 6，表明TG中角膜和鼻神经元的高共定位。结论 经鼻给予PVCL - PVA - PEG纳米胶束制剂能够有效地递送至TG神经元，并且它可能是治疗病理性TG神经元的一种有前景的疗法。
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