Highly cationic cell-penetrating peptides affect the barrier integrity and facilitates mannitol permeation in a human stem cell-based blood-brain barrier model

Research output: Contribution to journalJournal articlepeer-review

Standard

Highly cationic cell-penetrating peptides affect the barrier integrity and facilitates mannitol permeation in a human stem cell-based blood-brain barrier model. / Frøslev, Patrick; Franzyk, Henrik; Ozgür, Burak; Larsen, Birger Brodin; Kristensen, Mie.

In: European Journal of Pharmaceutical Sciences, Vol. 168, 106054, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Frøslev, P, Franzyk, H, Ozgür, B, Larsen, BB & Kristensen, M 2022, 'Highly cationic cell-penetrating peptides affect the barrier integrity and facilitates mannitol permeation in a human stem cell-based blood-brain barrier model', European Journal of Pharmaceutical Sciences, vol. 168, 106054. https://doi.org/10.1016/j.ejps.2021.106054

APA

Frøslev, P., Franzyk, H., Ozgür, B., Larsen, B. B., & Kristensen, M. (2022). Highly cationic cell-penetrating peptides affect the barrier integrity and facilitates mannitol permeation in a human stem cell-based blood-brain barrier model. European Journal of Pharmaceutical Sciences, 168, [106054]. https://doi.org/10.1016/j.ejps.2021.106054

Vancouver

Frøslev P, Franzyk H, Ozgür B, Larsen BB, Kristensen M. Highly cationic cell-penetrating peptides affect the barrier integrity and facilitates mannitol permeation in a human stem cell-based blood-brain barrier model. European Journal of Pharmaceutical Sciences. 2022;168. 106054. https://doi.org/10.1016/j.ejps.2021.106054

Author

Frøslev, Patrick ; Franzyk, Henrik ; Ozgür, Burak ; Larsen, Birger Brodin ; Kristensen, Mie. / Highly cationic cell-penetrating peptides affect the barrier integrity and facilitates mannitol permeation in a human stem cell-based blood-brain barrier model. In: European Journal of Pharmaceutical Sciences. 2022 ; Vol. 168.

Bibtex

@article{135b82e68246438b8b7b02cf93c84e66,
title = "Highly cationic cell-penetrating peptides affect the barrier integrity and facilitates mannitol permeation in a human stem cell-based blood-brain barrier model",
abstract = "The blood-brain barrier (BBB) allows passive permeation of only a limited number of, primarily lipophilic, low-molecular weight drugs that obey the so-called “rule of CNS likeness”. Therefore, novel strategies to facilitate drug delivery across the BBB are needed. Cell-penetrating peptides (CPPs) enable delivery of various therapeutic cargoes into cells and may potentially serve as shuttles for delivery of brain-specific drugs across the BBB. The CPPs Tat47–57 and penetratin are prototypical cationic CPPs, whereas apidaecin and oncocin belong to the group of proline-rich cationic antimicrobial peptides displaying CPP-like properties.The aim of the present study was to investigate the potential of Tat47–57, penetratin, apidaecin, and oncocin for interaction with and permeation of the BBB in vitro. We also studied whether the CPPs facilitated permeation of the paracellular flux marker mannitol as well as the transcellular flux marker propranolol. The peptides were labelled with the fluorophore 6-TAMRA (T) for visualization and quantification purposes. CPP membrane-adherence, membrane-embedding, and cellular uptake as well as barrier-permeation were evaluated in murine brain capillary endothelial cells (bEND3) and human induced pluripotent stem cell-derived (Bioni-010c) brain capillary endothelial-like monolayers. The cationic and the proline-rich cationic CPPs were taken up into the Bioni-010c monolayers. T-Tat47–57, T-apidaecin, and T-oncocin also permeated Bioni-010c monolayers, whereas T-penetratin did not. However, both T-Tat47–57 and T-penetratin affected the barrier integrity to a degree that facilitated permeation of 14C-mannitol. These results may therefore pave the way for future CPP-mediated brain delivery of small drugs that do not obey the “rule of CNS likeness”.",
author = "Patrick Fr{\o}slev and Henrik Franzyk and Burak Ozg{\"u}r and Larsen, {Birger Brodin} and Mie Kristensen",
year = "2022",
doi = "10.1016/j.ejps.2021.106054",
language = "English",
volume = "168",
journal = "Norvegica Pharmaceutica Acta",
issn = "0928-0987",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Highly cationic cell-penetrating peptides affect the barrier integrity and facilitates mannitol permeation in a human stem cell-based blood-brain barrier model

AU - Frøslev, Patrick

AU - Franzyk, Henrik

AU - Ozgür, Burak

AU - Larsen, Birger Brodin

AU - Kristensen, Mie

PY - 2022

Y1 - 2022

N2 - The blood-brain barrier (BBB) allows passive permeation of only a limited number of, primarily lipophilic, low-molecular weight drugs that obey the so-called “rule of CNS likeness”. Therefore, novel strategies to facilitate drug delivery across the BBB are needed. Cell-penetrating peptides (CPPs) enable delivery of various therapeutic cargoes into cells and may potentially serve as shuttles for delivery of brain-specific drugs across the BBB. The CPPs Tat47–57 and penetratin are prototypical cationic CPPs, whereas apidaecin and oncocin belong to the group of proline-rich cationic antimicrobial peptides displaying CPP-like properties.The aim of the present study was to investigate the potential of Tat47–57, penetratin, apidaecin, and oncocin for interaction with and permeation of the BBB in vitro. We also studied whether the CPPs facilitated permeation of the paracellular flux marker mannitol as well as the transcellular flux marker propranolol. The peptides were labelled with the fluorophore 6-TAMRA (T) for visualization and quantification purposes. CPP membrane-adherence, membrane-embedding, and cellular uptake as well as barrier-permeation were evaluated in murine brain capillary endothelial cells (bEND3) and human induced pluripotent stem cell-derived (Bioni-010c) brain capillary endothelial-like monolayers. The cationic and the proline-rich cationic CPPs were taken up into the Bioni-010c monolayers. T-Tat47–57, T-apidaecin, and T-oncocin also permeated Bioni-010c monolayers, whereas T-penetratin did not. However, both T-Tat47–57 and T-penetratin affected the barrier integrity to a degree that facilitated permeation of 14C-mannitol. These results may therefore pave the way for future CPP-mediated brain delivery of small drugs that do not obey the “rule of CNS likeness”.

AB - The blood-brain barrier (BBB) allows passive permeation of only a limited number of, primarily lipophilic, low-molecular weight drugs that obey the so-called “rule of CNS likeness”. Therefore, novel strategies to facilitate drug delivery across the BBB are needed. Cell-penetrating peptides (CPPs) enable delivery of various therapeutic cargoes into cells and may potentially serve as shuttles for delivery of brain-specific drugs across the BBB. The CPPs Tat47–57 and penetratin are prototypical cationic CPPs, whereas apidaecin and oncocin belong to the group of proline-rich cationic antimicrobial peptides displaying CPP-like properties.The aim of the present study was to investigate the potential of Tat47–57, penetratin, apidaecin, and oncocin for interaction with and permeation of the BBB in vitro. We also studied whether the CPPs facilitated permeation of the paracellular flux marker mannitol as well as the transcellular flux marker propranolol. The peptides were labelled with the fluorophore 6-TAMRA (T) for visualization and quantification purposes. CPP membrane-adherence, membrane-embedding, and cellular uptake as well as barrier-permeation were evaluated in murine brain capillary endothelial cells (bEND3) and human induced pluripotent stem cell-derived (Bioni-010c) brain capillary endothelial-like monolayers. The cationic and the proline-rich cationic CPPs were taken up into the Bioni-010c monolayers. T-Tat47–57, T-apidaecin, and T-oncocin also permeated Bioni-010c monolayers, whereas T-penetratin did not. However, both T-Tat47–57 and T-penetratin affected the barrier integrity to a degree that facilitated permeation of 14C-mannitol. These results may therefore pave the way for future CPP-mediated brain delivery of small drugs that do not obey the “rule of CNS likeness”.

U2 - 10.1016/j.ejps.2021.106054

DO - 10.1016/j.ejps.2021.106054

M3 - Journal article

C2 - 34728364

VL - 168

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

M1 - 106054

ER -

ID: 283126867