Aerosolized In Vivo 3D Localization of Nose-to-Brain Nanocarrier Delivery Using Multimodality Neuroimaging in a Rat Model—Protocol Development
| Autor: | Chin-Tu Chen, Michael W. Vannier, Marta Zamora, Sudip Kumar Das, Shih-Hsun Cheng, Hamideh Zarrinmayeh, Michael C. Veronesi, Brian D Graner |
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| Rok vydání: | 2021 |
| Předmět: |
positron emission tomography
PET/CT lcsh:RS1-441 Pharmaceutical Science 02 engineering and technology aerosolized drug delivery Article lcsh:Pharmacy and materia medica hybrid nanoparticles 03 medical and health sciences Neuroimaging In vivo medicine intranasal delivery 030304 developmental biology 0303 health sciences PET-CT nanotechnology medicine.diagnostic_test business.industry nose to brain delivery molecular imaging 021001 nanoscience & nanotechnology medicine.anatomical_structure Positron emission tomography fate mapping Nasal administration Molecular imaging 0210 nano-technology business Olfactory epithelium Ex vivo Biomedical engineering |
| Zdroj: | Pharmaceutics Pharmaceutics, Vol 13, Iss 391, p 391 (2021) Volume 13 Issue 3 |
| ISSN: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics13030391 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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