@article{oai:nagasaki-u.repo.nii.ac.jp:00027921,
 author = {Kato, Naoya and Yamada, Sakura and Suzuki, Rino and Iida, Yoshiki and Matsumoto, Makoto and Fumoto, Shintaro and Arima, Hidetoshi and Mukai, Hidefumi and Kawakami, Shigeru},
 issue = {1},
 journal = {Drug Delivery},
 month = {Jan},
 note = {Liposomes are versatile carriers that can encapsulate various drugs; however, for delivery to the brain, they must be modified with a targeting ligand or other modifications to provide blood–brain barrier (BBB) permeability, while avoiding rapid clearance by reticuloendothelial systems through polyethylene glycol (PEG) modification. BBB-penetrating peptides act as brain-targeting ligands. In this study, to achieve efficient brain delivery of liposomes, we screened the functionality of eight BBB-penetrating peptides reported previously, based on high-throughput quantitative evaluation methods with in vitro BBB permeability evaluation system using Transwell, in situ brain perfusion system, and others. For apolipoprotein E mimetic tandem dimer peptide (ApoEdp), which showed the best brain-targeting and BBB permeability in the comparative evaluation of eight peptides, its lipid conjugate with serine–glycine (SG)5 spacer (ApoEdp-SG-lipid) was newly synthesized and ApoEdp-modified PEGylated liposomes were prepared. ApoEdp-modified PEGylated liposomes were effectively associated with human brain capillary endothelial cells via the ApoEdp sequence and permeated the membrane in an in vitro BBB model. Moreover, ApoEdp-modified PEGylated liposomes accumulated in the brain 3.9-fold higher than PEGylated liposomes in mice. In addition, the ability of ApoEdp-modified PEGylated liposomes to localize beyond the BBB into the brain parenchyma in mice was demonstrated via three-dimensional imaging with tissue clearing. These results suggest that ApoEdp-SG-lipid modification is an effective approach for endowing PEGylated liposomes with the brain-targeting ability and BBB permeability., Drug Delivery, 30(1), art. no. 2173333; 2023},
 title = {Development of an apolipoprotein E mimetic peptide–lipid conjugate for efficient brain delivery of liposomes},
 volume = {30},
 year = {2023}
}