Amphiphilic Copolymers Shuttle Drugs Across the Blood-Brain Barrier

Macromolecular Bioscience
Mirjam Clemens-HemmelmannRudolf Zentel

Abstract

Medical treatment of diseases of the central nervous system requires transport of drugs across the blood-brain barrier (BBB). Here, it is extended previously in vitro experiments with a model compound to show that the non-water-soluble and brain-impermeable drug domperidone (DOM) itself can be enriched in the brain by use of an amphiphilic copolymer as a carrier. This carrier consists of poly(N-(2-hydroxypropyl)-methacrylamide), statistically copolymerized with 10 mol% hydrophobic lauryl methacrylate, into whose micellar aggregates DOM is noncovalently absorbed. As tested in a BBB model efficient transport of DOM across, the BBB is achievable over a wide range of formulations, containing 0.8 to 35.5 wt% domperidone per copolymer. In neither case, the polymer itself is translocated across the BBB model. In vivo experiments in mice show that already 10 min after intraperitoneal injection of the polymer/domperidone (PolyDOM) formulation, domperidone can be detected in blood and in the brain. Highest serum and brain levels of domperidone are detected 40 min after injection. At that time point serum domperidone is increased 48-fold. Most importantly, domperidone is exclusively detectable in high amounts in the brain of PolyDOM injec...Continue Reading

References

Jun 6, 2000·Advanced Drug Delivery Reviews·A H Schinkel
Mar 17, 2001·Advanced Drug Delivery Reviews·J Kreuter
Jan 22, 2003·Advanced Drug Delivery Reviews·Alexander V KabanovDonald W Miller
Mar 3, 2004·Molecular Interventions·William M Pardridge
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Wolfgang Löscher, Heidrun Potschka
Jul 19, 2005·Nature Reviews. Neuroscience·Wolfgang Löscher, Heidrun Potschka
Feb 6, 2008·Expert Opinion on Drug Delivery·Giovanni TosiMaria Angela Vandelli
Jun 7, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Elena V Batrakova, Alexander V Kabanov
Aug 12, 2009·Neurobiology of Disease·N Joan AbbottDavid J Begley
Sep 4, 2009·European Journal of Clinical Pharmacology·Bradley L Urquhart, Richard B Kim
Nov 17, 2009·Advanced Drug Delivery Reviews·Xin-Ming LiuDong Wang
Nov 28, 2009·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Tapan ParikhEmilio Squillante
Feb 18, 2010·Medicinal Research Reviews·Christian CeliaMassimo Fresta
Jan 1, 2007·Progress in Polymer Science·A V Kabanov, H E Gendelman
Apr 7, 2011·Macromolecular Rapid Communications·Mirjam HemmelmannRudolf Zentel
Sep 18, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mirjam HemmelmannRudolf Zentel
Sep 6, 2013·Molecular Pharmaceutics·Mirjam HemmelmannManfred Schmidt
Mar 20, 2014·Macromolecular Bioscience·Lutz NuhnRudolf Zentel

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Citations

Jun 27, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Reham S ElezabyGehanne A Awad

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