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
Corresponding AuthorPuno, 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 PublicationPHARMACEUTICS
Volume11Issue:9Pages:16
AbstractThe 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.
Keywordblood-brain barrier (BBB) drug delivery transient modulation HAV6 cadherin peptide adenanthin magnetic resonance imaging (MRI) medulloblastoma
DOI10.3390/pharmaceutics11090481
Indexed BySCI ; SCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000489151700037
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://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 AuthorPuno, Pema-Tenzin; Vanan, Magimairajan Issai; Miller, Donald W.
Affiliation1.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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Sajesh, Babu, V]'s Articles
[On, Ngoc H.]'s Articles
[Omar, Refaat]'s Articles
Baidu academic
Similar articles in Baidu academic
[Sajesh, Babu, V]'s Articles
[On, Ngoc H.]'s Articles
[Omar, Refaat]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Sajesh, Babu, V]'s Articles
[On, Ngoc H.]'s Articles
[Omar, Refaat]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.