caa a22 4500 445312017 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0440-7 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0440-7 Cell-Penetrating Peptide-Modified Block Copolymer Micelles Promote Direct Brain Delivery via Intranasal Administration [Elektronische Daten] [Takanori Kanazawa, Hiroyuki Taki, Ko Tanaka, Yuuki Takashima, Hiroaki Okada] ABSTRACT: Purpose: In order to develop non-invasive and effective nose-to-brain delivery of drugs, we synthesized Tat analog-modified methoxy poly(ethylene glycol) (MPEG)/poly(ε-caprolactone) (PCL) amphiphilic block copolymers through the ester bond. Methods: We evaluated the brain distribution of coumarin, acting as a model chemical, after intravenous or intranasal administration of MPEG-PCL. In addition, cellular uptake of coumarin by rat glioma cells transfected with coumarin-loaded MPEG-PCL or MPEG-PCL-Tat was determined. Finally, we determined the brain distribution and biodistribution after intranasal administration of coumarin-loaded MPEG-PCL-Tat. Results: The amount of coumarin in the brain after intranasal administration was significantly higher than that after intravenous administration. In addition, cellular uptake of coumarin using MPEG-PCL was the lowest, while cellular uptake of coumarin using Tat-modified MPEG-PCL (MPEG-PCL-Tat) was higher than that of MPEG-PCL. Therefore, the brain distribution of coumarin administered using MPEG-PCL-Tat was significantly greater than that using MPEG-PCL. Then, the coumarin distribution after MPEG-PCL-Tat administration in non-targeted tissues (lung, liver, heart, kidney and spleen) was lower than that after coumarin administration without nanomicelles. Conclusion: We have demonstrated that utilization of nano-sized micelles modified with Tat can facilitate direct intranasal brain delivery. Springer Science+Business Media, LLC, 2011 biodistribution nationallicence brain tumors nationallicence cell penetrating peptide nationallicence intranasal brain delivery nationallicence micelles nationallicence Kanazawa Takanori Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut Taki Hiroyuki Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut Tanaka Ko Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut Takashima Yuuki Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut Okada Hiroaki Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2130-2139 0724-8741 28:9<2130 2011 28 11095 https://doi.org/10.1007/s11095-011-0440-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0440-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kanazawa Takanori Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut NATIONALLICENCE 700 1- Taki Hiroyuki Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut NATIONALLICENCE 700 1- Tanaka Ko Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut NATIONALLICENCE 700 1- Takashima Yuuki Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut NATIONALLICENCE 700 1- Okada Hiroaki Laboratory of Pharmaceutics and Drug Delivery Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, 192-0392, Hachioji, Tokyo, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2130-2139 0724-8741 28:9<2130 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer