TY - JOUR
T1 - Evaluation of Cell-Penetrating Peptides Using Microfluidic In Vitro 3D Brain Endothelial Barrier
AU - Chung, Bohye
AU - Kim, Jaehoon
AU - Nam, Jiyoung
AU - Kim, Hyunho
AU - Jeong, Yeju
AU - Liu, Hui wen
AU - Cho, Youngkyu
AU - Kim, Yong Ho
AU - Oh, Hyun Jeong
AU - Chung, Seok
N1 - Funding Information:
B.C. and J.K. contributed equally to this work. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2017M2A2A7A02019899 (for KU)/(2018M2A2A7A02067531 (for SKKU) and 2020R1C1C1011255). H.J. Oh was supported by a Korea University Grant.
Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/6/1
Y1 - 2020/6/1
N2 - In drug delivery to the human brain, blood vessels are a significant hurdle because they restrict the entry of most solutes to protect brain. To overcome this hurdle, an in vitro 3D model for brain endothelial barrier is developed using a microfluidic device with hydrogel providing a 3D extracellular matrix scaffold. Using the model, peptides known to utilize receptor-mediated transcytosis are verified, which has been one of the most promising mechanisms for brain-specific penetration. The cytotoxicity and cellular damage to the peptide are investigated and the receptor-mediated transcytosis and brain endothelial specific penetrating abilities of the peptides in a quantitative manner are demonstrated. As a preclinical test, applying the quantification assays conducted in this study are suggested, including the penetrating ability, cytotoxicity, endothelial damage, and receptor specificity. Using this microfluidic device as an in vitro platform for evaluating various brain targeting drugs and drug carrier candidates is also proposed.
AB - In drug delivery to the human brain, blood vessels are a significant hurdle because they restrict the entry of most solutes to protect brain. To overcome this hurdle, an in vitro 3D model for brain endothelial barrier is developed using a microfluidic device with hydrogel providing a 3D extracellular matrix scaffold. Using the model, peptides known to utilize receptor-mediated transcytosis are verified, which has been one of the most promising mechanisms for brain-specific penetration. The cytotoxicity and cellular damage to the peptide are investigated and the receptor-mediated transcytosis and brain endothelial specific penetrating abilities of the peptides in a quantitative manner are demonstrated. As a preclinical test, applying the quantification assays conducted in this study are suggested, including the penetrating ability, cytotoxicity, endothelial damage, and receptor specificity. Using this microfluidic device as an in vitro platform for evaluating various brain targeting drugs and drug carrier candidates is also proposed.
KW - blood brain barrier
KW - cell-penetrating peptide
KW - receptor mediated transcytosis
UR - http://www.scopus.com/inward/record.url?scp=85084142147&partnerID=8YFLogxK
U2 - 10.1002/mabi.201900425
DO - 10.1002/mabi.201900425
M3 - Article
C2 - 32329170
AN - SCOPUS:85084142147
SN - 1616-5187
VL - 20
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 6
M1 - 1900425
ER -