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Inhibition of macrophage phagocytotic activity by a receptor-targeted polymer vesicle-based drug delivery formulation of pravastatin

Broz, P. and Ben-Haim, N. and Grzelakowski, M. and Marsch, S. and Meier, W. and Hunziker, P.. (2008) Inhibition of macrophage phagocytotic activity by a receptor-targeted polymer vesicle-based drug delivery formulation of pravastatin. Journal of cardiovascular pharmacology, Vol. 51, H. 3. pp. 246-252.

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Official URL: http://edoc.unibas.ch/dok/A6003556

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Abstract

Ruptures of macrophage-rich atherosclerotic plaques in the coronary arteries are the main reason for heart attack. Targeted therapeutic interventions with an inhibitory effect on the macrophages promise to be beneficial, but currently available drugs such as statins achieve event reductions of only 30%. Dose-limiting adverse effects in remote organs prohibit achieving higher drug levels known to have strong inhibitory effects on macrophages. Receptor-specific targeting using statin-loaded nanometer-sized triblock copolymer vesicles with targeting moieties might allow high-dose treatment for improved efficacy, while minimizing toxicity in other cells. Vesicle uptake by target cells but not other cell types and slow intracellular content release was observed. A major improvement in biologic efficacy was observed for polymer vesicles compared to free drug, whereas no increased cytotoxicity was observed in muscle cells. Such high-dose, targeted therapy of statins through cell-specific polymer vesicles allows novel treatment paradigms not only for atherosclerosis, but appears promising for a wide range of drugs and diseases.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Intensivmedizin > Intensivmedizin (Marsch)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Intensivmedizin > Intensivmedizin (Marsch)
UniBasel Contributors:Marsch, Stephan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Lippincott Williams & Wilkins
ISSN:0160-2446
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 Apr 2014 08:01
Deposited On:25 Apr 2014 08:01

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