Open AccessBrain Delivery of Multifunctional Dendrimer Protein Bioconjugates
Author(s) -
Moscariello Pierpaolo,
Ng David Y. W.,
Jansen Malin,
Weil Tanja,
Luhmann Heiko J.,
Hedrich Jana
Publication year - 2018
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201700897
Subject(s) - transcytosis , drug delivery , dendrimer , blood–brain barrier , in vivo , biotinylation , bioconjugation , chemistry , streptavidin , in vitro , nanomedicine , biophysics , nanotechnology , microbiology and biotechnology , central nervous system , neuroscience , biochemistry , biotin , materials science , biology , endocytosis , nanoparticle , cell
Neurological 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.