Abstract
Atherosclerosis results in the narrowing of arterial blood vessels and this causes significant changes in the endogenous shear stress between healthy and constricted arteries. Nanocontainers that can release drugs locally with such rheological changes can be very useful. Here, we show that vesicles made from an artificial 1,3-diaminophospholipid are stable under static conditions but release their contents at elevated shear stress. These vesicles have a lenticular morphology, which potentially leads to instabilities along their equator. Using a model cardiovascular system based on polymer tubes and an external pump to represent shear stress in healthy and constricted vessels of the heart, we show that drugs preferentially release from the vesicles in constricted vessels that have high shear stress.
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Acknowledgements
This work was supported by the Swiss National Science Foundation via Research Program 62 ‘Smart Materials’ and the proof-of-principle fund of the University of Geneva. I.A.F., P.-L.Z. and A.Z. acknowledge support from the Swiss National Science Foundation (grant 200020_132035) and European Cooperation in Science and Technology Action D43. The authors thank the Electron Microscopy Center ETH Zurich and T. Ishikawa for cryo-TEM work, K. Peters for viability tests, and the Bioimaging, Mass Spectroscopy and Nuclear Magnetic Resonance facilities at the University of Geneva for analytical services, and the Critical Care Service at the University Hospitals of Geneva for the gift of the extracorporeal heart pump. The authors also appreciate scientific discussions with T. Fyles, A. Roux, F. Stellacci and T. Zemb.
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B.M., T.S. and A.Z. contributed the original idea, secured the financing and supervised the project. M.N.H., B.M., T.S. and A.Z. designed the experiments. I.A.F. synthesized Pad–PC–Pad. M.N.H., I.A.F., D.A., J.A., L.B., F.F., R.R., R.T., P-L.Z., A.Zi. and A.Z. performed the experiments. M.N.H., R.R., A.Zi., B.M., T.S. and A.Z. wrote the paper.
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Holme, M., Fedotenko, I., Abegg, D. et al. Shear-stress sensitive lenticular vesicles for targeted drug delivery. Nature Nanotech 7, 536–543 (2012). https://doi.org/10.1038/nnano.2012.84
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DOI: https://doi.org/10.1038/nnano.2012.84
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