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Bode, Gerard H.; Coue, Gregory; Freese, Christian; Pickl, Karin E.; Sanchez-Purra, Maria; Albaiges, Berta; Borros, Salvador; Winden, Ewoud C. van; Tziveleka, Leto-Aikaterini; Sideratou, Zili; Engbersen, Johan F. J.; Singh, Smriti; Albrecht, Krystyna; Groll, Jürgen; Möller, Martin; Pötgens, Andy J. G.; Schmitzk, Christoph; Fröhlich, Eleonore; Grandfils, Christian; Sinner, Frank M.; Kirkpatrick, C. James; Steinbusch, Harry W. M.; Frank, Hans-Georg; Unger, Ronald E.; Martinez-Martinez, Pilar (2017): An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake. In: Nanomedicine-Nanotechnology Biology and Medicine, Vol. 13, No. 3: pp. 1289-1300
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Abstract

Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations.