Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

• DOI: 10.1002/advs.201700897
• Publication Date: 2018-02-23T08:40:38Z
• Authors: Pierpaolo Moscari...; David Y. W. Ng; Malin Jansen; Tanja Weil; Heiko J. Luhmann; Jana Hedrich
• Keywords: 0301 basic medicine; 03 medical and health sciences; Full Papers; 3. Good health

AbstractNeurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood‐brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) treatments are presented here. A poly(amido)amine (PAMAM) dendrimer bioconjugate with a streptavidin adapter for the attachment of dendrons or any biotinylated drug is constructed. In vitro studies on porcine or murine models and in vivo mouse studies are performed and reveal the permeation of dendronized streptavidin (DSA) into the CNS. The bioconjugate is taken up mainly by the caveolae pathway and transported across the BBB via transcytosis escaping from lysosomes. After transcytosis DSA are delivered to astrocytes and neurons. Furthermore, DSA offer high biocompatibility in vitro and in vivo. In summary, a new strategy for implementing therapeutic PAMAM function as well as drug delivery in neuropathology is presented here.