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Accepted (AM)Open Access (License Unspecified), Open
Journal article
A Supramolecular Nanocarrier for Delivery of Amiodarone Anti-Arrhythmic Therapy to the Heart
Bioconjugate chemistry, v 30(3), pp 733-740
20 Mar 2019
PMID: 30615425
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Amiodarone is an effective antiarrhythmic drug used to treat and prevent different types of cardiac arrhythmias. However, amiodarone can have considerable side effects resulting from accumulation in off-target tissues. Cardiac macrophages are highly prevalent tissue-resident immune cells with importance in homeostatic functions, including immune response and modulation of cardiac conduction. We hypothesized that amiodarone could be more efficiently delivered to the heart via cardiac macrophages, an important step toward reducing overall dose and off-target tissue accumulation. Toward this goal, we synthesized a nanoparticle drug carrier composed of l-lysine cross-linked succinyl-β-cyclodextrin that demonstrates amiodarone binding through supramolecular host-guest interaction as well as a high macrophage affinity. Biodistribution analyses at the organ and single-cell level demonstrate accumulation of nanoparticles in the heart resulting from rapid uptake by cardiac macrophages. Nanoparticle assisted delivery of amiodarone resulted in a 250% enhancement in the selective delivery of the drug to cardiac tissue in part due to a concomitant decrease of pulmonary accumulation, the main source of off-target toxicity.
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Details
- Title
- A Supramolecular Nanocarrier for Delivery of Amiodarone Anti-Arrhythmic Therapy to the Heart
- Creators
- Maaz S Ahmed - Center for Systems BiologyChristopher B Rodell - Center for Systems BiologyMaarten Hulsmans - Center for Systems BiologyRainer H Kohler - Center for Systems BiologyAaron D Aguirre - Center for Systems BiologyMatthias Nahrendorf - Department of Radiology, Massachusetts General Hospital, 55 Fruit St, Boston, Massachusetts 02114, United StatesRalph Weissleder - Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, Massachusetts 02115, United States
- Publication Details
- Bioconjugate chemistry, v 30(3), pp 733-740
- Publisher
- American Chemical Society; Washington, DC
- Grant note
- R35 HL139598 / NHLBI NIH HHS R01 HL131495 / NHLBI NIH HHS R21 EB026762 / NIBIB NIH HHS U01 CA206997 / NCI NIH HHS R01 HL144515 / NHLBI NIH HHS T32 CA079443 / NCI NIH HHS R01 CA206890 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000462260300027
- Scopus ID
- 2-s2.0-85060554801
- Other Identifier
- 991019176805504721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemical Research Methods
- Biochemistry & Molecular Biology
- Chemistry, Multidisciplinary
- Chemistry, Organic