文獻名: 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. Das3and Michael W. Vannier
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,
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 ratmodel to measure nose-to-brain delivery. A quantitative temporal and spatial testing protocol fornew radio-nanotheranostic agents was soughtin vivo. LPNPs labeled with a zirconium 89 (89Zr) PETtracer 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 (olfactorybulb, forebrain, and brainstem) were isolated. The activity in each brain region was measured forcomparison with the corresponding PET/CT region of interest via activity measurements. Serialimaging of the LPNPs (100 nm PLA–PEG–DSPE+89Zr) delivered intranasally via nasal tubingdemonstrated 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 countingand autoradiography. Although assessment of delivery from nose to brain is a promising approach,the technology has several limitations that require further development. An experimental protocolfor aerosolized intranasal delivery is presented herein, which may provide a platform for bettertargeting the olfactory epithelium
關(guān)鍵詞:intranasal delivery; positron emission tomography; hybrid nanoparticles; nose to brain
delivery; nanotechnology; fate mapping; molecular imaging; PET/CT; aerosolized drug delivery
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