| Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors | |
Sajesh, Babu, V1; On, Ngoc H.2; Omar, Refaat2; Alrushaid, Samaa3,4; Kopec, Brian M.5; Wang, Wei-Guang6; Sun, Han-Dong6 ; Lillico, Ryan3; Lakowski, Ted M.3; Siahaan, Teruna J.5; Davies, Neal M.7; Puno, Pema-Tenzin6; Vanan, Magimairajan Issai1,8; Miller, Donald W.2
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| Corresponding Author | Puno, Pema-Tenzin(punopematenzin@mail.kib.ac.cn) ; Vanan, Magimairajan Issai(mivanan@cancercare.mb.ca) ; Miller, Donald W.(donald.miller@umanitoba.ca) |
| 2019-09-01 | |
| Source Publication | PHARMACEUTICS
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| Volume | 11Issue:9Pages:16 |
| Abstract | 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. |
| Keyword | blood-brain barrier (BBB) drug delivery transient modulation HAV6 cadherin peptide adenanthin magnetic resonance imaging (MRI) medulloblastoma |
| DOI | 10.3390/pharmaceutics11090481 |
| Indexed By | SCI ; SCI |
| Language | 英语 |
| WOS ID | WOS:000489151700037 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.kib.ac.cn/handle/151853/69953 |
| Collection | 植物化学与西部植物资源持续利用国家重点实验室 |
| Corresponding Author | Puno, Pema-Tenzin; Vanan, Magimairajan Issai; Miller, Donald W. |
| Affiliation | 1.Univ Manitoba, Res Inst Oncol & Hematol, Winnipeg, MB R3E 0V9, Canada 2.Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB R3E 0T6, Canada 3.Univ Manitoba, Coll Pharm Pharmaceut Anal Lab, Winnipeg, MB R3E 0V9, Canada 4.Kuwait Univ, Fac Pharm, Dept Pharmaceut Chem, Safat 13110, Kuwait 5.Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66205 USA 6.Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China 7.Univ Alberta, Pharm & Pharmaceut Sci, Edmonton, AB T6G 2R3, Canada 8.Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada |
| Recommended Citation GB/T 7714 | Sajesh, Babu, V,On, Ngoc H.,Omar, Refaat,et al. Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors[J]. PHARMACEUTICS,2019,11(9):16. |
| APA | Sajesh, Babu, V.,On, Ngoc H..,Omar, Refaat.,Alrushaid, Samaa.,Kopec, Brian M..,...&Miller, Donald 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),16. |
| MLA | Sajesh, Babu, V,et al."Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors".PHARMACEUTICS 11.9(2019):16. |
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| Sajesh-2019-Validati（3895KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Application Full Text | |
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