Evaluation of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer nanomicelle for trigeminal ganglion neurons delivering with intranasal administration

ABSTRACT

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.

KEYWORDS:

• Trigeminal ganglion (TG) neuron
• cornea
• intranasal administration
• polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG)
• nanomicelle

Declaration of Interests

The authors declare no conflict of interest.

Funding

This research was supported by the National Natural Science Foundation of China (Project nos. 81770895, 81500751 and 81271036), the Natural Science Foundation of Shandong Province, China (project no. ZR2015PH062), and the key research project of Shandong Province, China (project no. 2015GSF118121).

Additional information

Funding

This research was supported by the National Natural Science Foundation of China (Project nos. 81770895, 81500751 and 81271036), the Natural Science Foundation of Shandong Province, China (project no. ZR2015PH062), and the key research project of Shandong Province, China (project no. 2015GSF118121).

Notes on contributors

Mengshuang Li

X.W. designed the research, M.L., M.X., K.S., F.S. and J.L. performed the experiments, M.L. and X.W. analyzed data, X.W. and M.L. participated in the discussion. X.W. wrote and revised the paper. Y.H. participated in revising the paper. All authors reviewed the manuscript.