Multimodal Clinical Imaging To Longitudinally Assess a Nanomedical Anti-Inflammatory Treatment in Experimental Atherosclerosis
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Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy.
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Injection of a single intravenous dose of glucocorticoid-encapsulated PEG liposomes in atherosclerotic rabbits led to a statistically significant reduction in the 18F-FDG-PET signal in atherosclerotic lesions 2 days after treatment.
“the injection of a single intravenous dose of glucocorticoid-encapsulated liposomes conjugated to polyethylene glycol (PEG) in atherosclerotic rabbits led to a statistically significant reduction in the surrogate inflammatory marker, the 18F-fludeoxyglucose (18F-FDG)–PET signal (FIG. 3a), in atherosclerotic lesions just 2 days after treatment82.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [82]
Non-invasive imaging can longitudinally monitor therapeutic response in a rabbit model of atherosclerosis after nanomedical treatment.
“This study shows the ability of non-invasive imaging to longitudinally monitor therapeutic response in a rabbit model of atherosclerosis after nanomedical treatment.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [82]
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- Authors
- Lobatto, M. E., Fayad, Z. A., Silvera, S., Vucic, E., Calcagno, C., Mani, V., Dickson, S. D., Nicolay, K., Banciu, M., Schiffelers, R. M., Metselaar, J. M., van Bloois, L., Wu, H.-S., Fallon, J. T., Rudd, J. H., Fuster, V., Fisher, E. A., Storm, G., & Mulder, W. J. M.
- Affiliations
- Utrecht University (NL)
- Translational and Molecular Imaging Institute and Imaging Science Laboratories, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029, United States, Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands, Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands, Department of Pathology, Mount Sinai School...
- Corresponding author
- Fayad, Zahi A.
- Mulder, Willem J. M.
- ORCID
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-11-08
- Volume
- 7
- Issue
- 6
- Pages
- 2020-2029
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC3345199
- OpenAlex
- W2080041249
- Cited by
- 170
- References
- 45
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 10 · 2023: 6 · 2022: 9 · 2021: 14 · 2020: 11 · 2019: 15 · 2018: 15 · 2017: 16 · 2016: 9 · 2015: 13 · 2014: 13 · 2013: 13 · 2012: 15
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- TU/e Research Portal (submittedVersion)
- Funders
- British Heart Foundation (PG/09/083/27667)
- Academy of Medical Sciences (AMS-SGCL1-Rudd)
- National Heart, Lung, and Blood Institute (R01HL078667, R01HL071021)
- National Cancer Institute (R24CA095823)
- National Institute of Biomedical Imaging and Bioengineering (R01EB009638)
- National Center for Research Resources (1 S10RR0 9145-01)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- atherosclerosis, prednisolone, nanomedicine, anti-inflammatory therapy, atherosclerotic plaque, 18F-FDG PET, dynamic contrast-enhanced MRI, longitudinal imaging, macrophage density, rabbit model, drug delivery monitoring
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Arteriosclerosis, Disease Models, Animal, Glucocorticoids, Liposomes, Longitudinal Studies, Magnetic Resonance Imaging, Male, Rabbits, Drug Delivery Systems, Positron-Emission Tomography, Nanomedicine
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