Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro
The blood–brain barrier (BBB) poses major challenges to drug delivery to the CNS. SFTI-1 and kalata B1 are cyclic cell-penetrating peptides (cCPPs) with high potential to be used as scaffolds for drug delivery. We here studied their transport across the BBB and distribution within the brain to gauge...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1507 |
| _version_ | 1797598600229814272 |
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| author | Erik Melander Camilla Eriksson Sara Wellens Kimia Hosseini Robert Fredriksson Fabien Gosselet Maxime Culot Ulf Göransson Margareta Hammarlund-Udenaes Irena Loryan |
| author_facet | Erik Melander Camilla Eriksson Sara Wellens Kimia Hosseini Robert Fredriksson Fabien Gosselet Maxime Culot Ulf Göransson Margareta Hammarlund-Udenaes Irena Loryan |
| author_sort | Erik Melander |
| collection | DOAJ |
| description | The blood–brain barrier (BBB) poses major challenges to drug delivery to the CNS. SFTI-1 and kalata B1 are cyclic cell-penetrating peptides (cCPPs) with high potential to be used as scaffolds for drug delivery. We here studied their transport across the BBB and distribution within the brain to gauge the potential of these two cCPPs as scaffolds for CNS drugs. In a rat model, SFTI-1 exhibited, for a peptide, high extent of BBB transport with a partitioning of unbound SFTI-1 across the BBB, K<sub>p,uu,brain</sub>, of 13%, while only 0.5% of kalata B1 equilibrated across the BBB. By contrast, kalata B1, but not SFTI-1, readily entered neural cells. SFTI-1, but not kalata B1, could be a potential CNS delivery scaffold for drugs directed to extracellular targets. These findings indicate that differences between the BBB transport and cellular uptake abilities of CPPs are crucial in the development of peptide scaffolds. |
| first_indexed | 2024-03-11T03:24:25Z |
| format | Article |
| id | doaj.art-70dd2b1bd6a84387b9eff29521e5c9e8 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:25Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-70dd2b1bd6a84387b9eff29521e5c9e82023-11-18T02:52:36ZengMDPI AGPharmaceutics1999-49232023-05-01155150710.3390/pharmaceutics15051507Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In VitroErik Melander0Camilla Eriksson1Sara Wellens2Kimia Hosseini3Robert Fredriksson4Fabien Gosselet5Maxime Culot6Ulf Göransson7Margareta Hammarlund-Udenaes8Irena Loryan9Department of Pharmacy, Uppsala University, 75123 Uppsala, SwedenDepartment of Pharmaceutical Biosciences, Uppsala University, 75123 Uppsala, SwedenLaboratoire de la Barrière Hémato-Encéphalique (LBHE), Faculté des Sciences Jean Perrin, University of Artois, UR 2465, Rue Jean Souvraz SP18, F-62300 Lens, FranceDepartment of Pharmaceutical Biosciences, Uppsala University, 75123 Uppsala, SwedenDepartment of Pharmaceutical Biosciences, Uppsala University, 75123 Uppsala, SwedenLaboratoire de la Barrière Hémato-Encéphalique (LBHE), Faculté des Sciences Jean Perrin, University of Artois, UR 2465, Rue Jean Souvraz SP18, F-62300 Lens, FranceLaboratoire de la Barrière Hémato-Encéphalique (LBHE), Faculté des Sciences Jean Perrin, University of Artois, UR 2465, Rue Jean Souvraz SP18, F-62300 Lens, FranceDepartment of Pharmaceutical Biosciences, Uppsala University, 75123 Uppsala, SwedenDepartment of Pharmacy, Uppsala University, 75123 Uppsala, SwedenDepartment of Pharmacy, Uppsala University, 75123 Uppsala, SwedenThe blood–brain barrier (BBB) poses major challenges to drug delivery to the CNS. SFTI-1 and kalata B1 are cyclic cell-penetrating peptides (cCPPs) with high potential to be used as scaffolds for drug delivery. We here studied their transport across the BBB and distribution within the brain to gauge the potential of these two cCPPs as scaffolds for CNS drugs. In a rat model, SFTI-1 exhibited, for a peptide, high extent of BBB transport with a partitioning of unbound SFTI-1 across the BBB, K<sub>p,uu,brain</sub>, of 13%, while only 0.5% of kalata B1 equilibrated across the BBB. By contrast, kalata B1, but not SFTI-1, readily entered neural cells. SFTI-1, but not kalata B1, could be a potential CNS delivery scaffold for drugs directed to extracellular targets. These findings indicate that differences between the BBB transport and cellular uptake abilities of CPPs are crucial in the development of peptide scaffolds.https://www.mdpi.com/1999-4923/15/5/1507cyclic peptidecell-penetrating peptidekalata B1SFTI-1blood–brain barrierintracellular distribution |
| spellingShingle | Erik Melander Camilla Eriksson Sara Wellens Kimia Hosseini Robert Fredriksson Fabien Gosselet Maxime Culot Ulf Göransson Margareta Hammarlund-Udenaes Irena Loryan Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro Pharmaceutics cyclic peptide cell-penetrating peptide kalata B1 SFTI-1 blood–brain barrier intracellular distribution |
| title | Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro |
| title_full | Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro |
| title_fullStr | Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro |
| title_full_unstemmed | Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro |
| title_short | Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro |
| title_sort | differential blood brain barrier transport and cell uptake of cyclic peptides in vivo and in vitro |
| topic | cyclic peptide cell-penetrating peptide kalata B1 SFTI-1 blood–brain barrier intracellular distribution |
| url | https://www.mdpi.com/1999-4923/15/5/1507 |
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