PMID- 33002523 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20210617 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 328 DP - 2020 Dec 10 TI - Lactose-appended beta-cyclodextrin as an effective nanocarrier for brain delivery. PG - 722-735 LID - S0168-3659(20)30559-9 [pii] LID - 10.1016/j.jconrel.2020.09.043 [doi] AB - The blood-brain barrier (BBB) prevents the permeability of drugs into the brain, and as such limits the management of various brain diseases. To overcome this barrier, drug-encapsulating nanoparticles or vesicles, drug conjugates, and other types of drug delivery systems (DDSs) have been developed. However, the brain-targeting ability of nanoparticles or vesicles is still insufficient. Recently, among the various brain-targeting ligands previously studied for facilitating transcellular BBB transport, several sugar-appended nanocarriers for brain delivery were identified. Meanwhile, cyclodextrins (CyDs) have been used as nanocarriers for drug delivery since they can encapsulate hydrophobic compounds with high biocompatibility. Therefore, in this study, we created various sugar-appended beta-cyclodextrins (beta-CyDs) to discover novel brain-targeting ligands. As a result, of the six sugar-appended CyDs, lactose-appended beta-CyD (Lac-beta-CyD) showed greater cellular uptake in hCMEC/D3 cells, human brain microvascular endothelial cells, than other sugar-appended beta-CyDs did. In addition, the permeability of Lac-beta-CyD within the in vitro human BBB model was greater than that of other sugar-appended beta-CyDs. Moreover, Lac-beta-CyD significantly accumulated in the mouse brain after intravenous administration. Thus, Lac-beta-CyD efficiently facilitated the accumulation of the model drug into the mouse brain. These findings suggest that Lac-beta-CyD has the potential to be a novel carrier for drugs across the BBB. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Yokoyama, Ryoma AU - Yokoyama R AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Taharabaru, Toru AU - Taharabaru T AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Nishida, Takumi AU - Nishida T AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Ohno, Yoshitaka AU - Ohno Y AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Maeda, Yuki AU - Maeda Y AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Sato, Masahiro AU - Sato M AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Ishikura, Kandai AU - Ishikura K AD - Research Institute of Nihon Shokuhin Kako Co., Ltd, 30 Tajima, Fuji, Shizuoka 417-8530, Japan. FAU - Yanagihara, Kazunori AU - Yanagihara K AD - Research Institute of Nihon Shokuhin Kako Co., Ltd, 30 Tajima, Fuji, Shizuoka 417-8530, Japan. FAU - Takagi, Hiroki AU - Takagi H AD - Research Institute of Nihon Shokuhin Kako Co., Ltd, 30 Tajima, Fuji, Shizuoka 417-8530, Japan. FAU - Nakamura, Teruya AU - Nakamura T AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Priority Organization for Innovation and Excellence, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Ito, Shingo AU - Ito S AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Ohtsuki, Sumio AU - Ohtsuki S AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Arima, Hidetoshi AU - Arima H AD - Laboratory of Evidence-Based Pharmacotherapy, Daiichi University of Pharmacy, 22-1 Tamagawa-machi, Minami-ku, Fukuoka 815-8511, Japan. FAU - Onodera, Risako AU - Onodera R AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Higashi, Taishi AU - Higashi T AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Priority Organization for Innovation and Excellence, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. FAU - Motoyama, Keiichi AU - Motoyama K AD - Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address: motoyama@kumamoto-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200928 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Cyclodextrins) RN - 0 (beta-Cyclodextrins) RN - J2B2A4N98G (Lactose) SB - IM MH - Brain MH - *Cyclodextrins MH - Endothelial Cells MH - Lactose MH - *beta-Cyclodextrins OTO - NOTNLM OT - Blood-brain barrier OT - Brain delivery OT - Brain targeting OT - Cyclodextrin OT - Lactose EDAT- 2020/10/02 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/10/01 20:11 PHST- 2020/06/09 00:00 [received] PHST- 2020/09/15 00:00 [revised] PHST- 2020/09/23 00:00 [accepted] PHST- 2020/10/02 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/10/01 20:11 [entrez] AID - S0168-3659(20)30559-9 [pii] AID - 10.1016/j.jconrel.2020.09.043 [doi] PST - ppublish SO - J Control Release. 2020 Dec 10;328:722-735. doi: 10.1016/j.jconrel.2020.09.043. Epub 2020 Sep 28.