文献名：Aerosolized In Vivo 3D Localization of Nose-to-Brain Nanocarrier Delivery Using Multimodality Neuroimaging in a Rat Model—Protocol Development

作者： Michael C. Veronesi¹, Brian D. Graner¹, Shih-Hsun Cheng², Marta Zamora², Hamideh Zarrinmayeh¹, Chin-Tu Chen², Sudip K. Das³ and Michael W. Vannier²

¹The Department of Radiology and Imaging Sciences, School of Medicine, Indiana University Indianapolis, Indianapolis, IN 46202, USA

²The Department of Radiology, University of Chicago, Chicago, IL 60637, USA

³The Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, Butler University, Indianapolis, IN 46208, USA

摘要：The fate of intranasal aerosolized radiolabeled polymeric micellar nanoparticles (LPNPs) was tracked with positron emission tomography/computer tomography (PET/CT) imaging in a rat model to measure nose-to-brain delivery. A quantitative temporal and spatial testing protocol for new radio-nanotheranostic agents was sought in vivo. LPNPs labeled with a zirconium 89 (⁸⁹Zr) PET tracer were administered via intranasal or intravenous delivery, followed by serial PET/CT imaging. After 2 h of continuous imaging, the animals were sacrificed, and the brain substructures (olfactory bulb, forebrain, and brainstem) were isolated. The activity in each brain region was measured for comparison with the corresponding PET/CT region of interest via activity measurements. Serial imaging of the LPNPs (100 nm PLA–PEG–DSPE+⁸⁹Zr) delivered intranasally via nasal tubing demonstrated increased activity in the brain after 1 and 2 h following intranasal drug delivery (INDD) compared to intravenous administration, which correlated with ex vivo gamma counting and autoradiography. Although assessment of delivery from nose to brain is a promising approach, the technology has several limitations that require further development. An experimental protocol for aerosolized intranasal delivery is presented herein, which may provide a platform for better targeting the olfactory epithelium

关键词：intranasal delivery; positron emission tomography; hybrid nanoparticles; nose to brain delivery; nanotechnology; fate mapping; molecular imaging; PET/CT; aerosolized drug delivery