دورية أكاديمية
Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors
| العنوان: | Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors |
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| المؤلفون: | Sajesh, Babu V., On, Ngoc H., Omar, Refaat, Alrushaid, Samaa, Kopec, Brian M., Wang, Wei-Guang, Sun, Han-Dong, Lillico, Ryan, Lakowski, Ted M., Siahaan, Teruna J., Davies, Neal M., Puno, Pema-Tenzin, Vanan, Magimairajan Issai, Miller, Donald W. |
| بيانات النشر: | MDPI |
| سنة النشر: | 2019 |
| المجموعة: | The University of Kansas: KU ScholarWorks |
| مصطلحات موضوعية: | Blood-brain barrier (BBB), Drug delivery, Transient modulation, HAV6 cadherin peptide, Adenanthin, Magnetic resonance imaging (MRI), Medulloblastoma |
| الوصف: | This work is licensed under a Creative Commons Attribution 4.0 International License. ; The blood-brain barrier (BBB) poses a major obstacle by preventing potential therapeutic agents from reaching their intended brain targets at sufficient concentrations. While transient disruption of the BBB has been used to enhance chemotherapeutic efficacy in treating brain tumors, limitations in terms of magnitude and duration of BBB disruption exist. In the present study, the preliminary safety and efficacy profile of HAV6, a peptide that binds to the external domains of cadherin, to transiently open the BBB and improve the delivery of a therapeutic agent, was evaluated in a murine brain tumor model. Transient opening of the BBB in response to HAV6 peptide administration was quantitatively characterized using both a gadolinium magnetic resonance imaging (MRI) contrast agent and adenanthin (Ade), the intended therapeutic agent. The effects of HAV6 peptide on BBB integrity and the efficacy of concurrent administration of HAV6 peptide and the small molecule inhibitor, Ade, in the growth and progression of an orthotopic medulloblastoma mouse model using human D425 tumor cells was examined. Systemic administration of HAV6 peptide caused transient, reversible disruption of BBB in mice. Increases in BBB permeability produced by HAV6 were rapid in onset and observed in all regions of the brain examined. Concurrent administration of HAV6 peptide with Ade, a BBB impermeable inhibitor of Peroxiredoxin-1, caused reduced tumor growth and increased survival in mice bearing medulloblastoma. The rapid onset and transient nature of the BBB modulation produced with the HAV6 peptide along with its uniform disruption and biocompatibility is well-suited for CNS drug delivery applications, especially in the treatment of brain tumors. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | Sajesh, B. V., On, N. H., Omar, R., Alrushaid, S., Kopec, B. M., Wang, W. G., Sun, H. D., Lillico, R., Lakowski, T. M., Siahaan, T. J., Davies, N. M., Puno, P. T., Vanan, M. I., & Miller, D. W. (2019). Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors. Pharmaceutics, 11(9), 481. https://doi.org/10.3390/pharmaceutics11090481Test; http://hdl.handle.net/1808/30421Test; orcid:0000-0001-7705-9025; orcid:0000-0002-1029-2188; orcid:0000-0002-9486-9254; orcid:0000-0002-7050-1471; orcid:0000-0001-5212-3000; orcid:0000-0003-2015-0615; orcid:0000-0003-1952-5635; PMC6781504 |
| DOI: | 10.3390/pharmaceutics11090481 |
| الإتاحة: | https://doi.org/10.3390/pharmaceutics11090481Test http://hdl.handle.net/1808/30421Test |
| حقوق: | © 2019 by the authors. Licensee MDPI, Basel, Switzerland. ; http://creativecommons.org/licenses/by/4.0Test/ ; openAccess |
| رقم الانضمام: | edsbas.DD146B10 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/pharmaceutics11090481 |
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