Crossing the blood-brain barrier: Glutathione-conjugated poly(ethylene imine) for gene delivery
| Autor: | Philipp S. Borchers, Martin Raasch, Alexander S. Mosig, Tanja Bus, Anne-Kristin Trützschler, Ulrich S. Schubert, Anja Traeger, Christoph Englert |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Survival Imine Pharmaceutical Science Biocompatible Materials 02 engineering and technology Gene delivery Conjugated system Blood–brain barrier 03 medical and health sciences chemistry.chemical_compound Mice medicine Animals Humans Polyethyleneimine Drug Carriers Gene Transfer Techniques Endothelial Cells Glutathione 021001 nanoscience & nanotechnology 030104 developmental biology medicine.anatomical_structure HEK293 Cells chemistry Transcytosis Biochemistry Targeted drug delivery Microscopy Fluorescence Blood-Brain Barrier Biophysics Nanocarriers 0210 nano-technology |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 241 |
| ISSN: | 1873-4995 |
| Popis: | The targeted drug delivery to the central nervous system represents one of the major challenges in pharmaceutical formulations since it is strictly limited through the highly selective blood-brain barrier (BBB). l-Glutathione (GSH), a tripeptide and well-known antioxidant, has been studied in the last years as potential candidate to facilitate the receptor-mediated transcytosis of nanocarriers. We thus tested whether GSH decoration of a positively charged polymer, poly(ethylene imine), with this vector enables the transport of genetic material and, simultaneously, the passage through the BBB. In this study, we report the synthesis of GSH conjugated cationic poly(ethylene imine)s via ecologically desirable thiol-ene photo-addition. The copolymers, containing 80% primary or secondary amine groups, respectively, were investigated concerning their bio- and hemocompatibility as well as their ability to cross a hCMEC/D3 endothelial cell layer mimicking the BBB within microfluidically perfused biochips. We demonstrate that BBB passage depends on the used amino-groups and on the GSH ratio. Thereby the copolymer containing secondary amines showed an enhanced performance. We thus conclude that GSH-coupling represents a feasible and promising approach for the functionalization of nanocarriers intended to cross the BBB for the delivery of drugs to the central nervous system. |
| Databáze: | OpenAIRE |
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