2019
DOI: 10.3390/pharmaceutics11110568
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Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides

Abstract: Many proteins can be used to treat brain diseases; however, the presence of the blood–brain barrier (BBB) creates an obstacle to delivering them into the brain. Previously, various molecules were delivered through the paracellular pathway of the BBB via its modulation, using ADTC5 and HAV6 peptides. This study goal was to design new cyclic peptides with N-to-C terminal cyclization for better plasma stability and modulation of the BBB. Cyclic HAVN1 and HAVN2 peptides were derived from a linear HAV6 peptide. Lin… Show more

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Cited by 19 publications
(42 citation statements)
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“…Antibodies hold a fundamental place in cancer immunotherapy strategies. However, the BBB limits the passage of most of the large molecules such as mAbs [ 196 ]. Many physicochemical properties determine the ability of a compound to pass the BBB (e.g., size, lipophilicity, molecular weight, degree of hydrogen bonding) and the delivery of many drugs across the BBB is consequently insufficient [ 198 ].…”
Section: Limitations Of Current Preclinical Models and Future Outlook To Improve Combination Strategies For The Immunotherapy Of Gbmmentioning
confidence: 99%
See 1 more Smart Citation
“…Antibodies hold a fundamental place in cancer immunotherapy strategies. However, the BBB limits the passage of most of the large molecules such as mAbs [ 196 ]. Many physicochemical properties determine the ability of a compound to pass the BBB (e.g., size, lipophilicity, molecular weight, degree of hydrogen bonding) and the delivery of many drugs across the BBB is consequently insufficient [ 198 ].…”
Section: Limitations Of Current Preclinical Models and Future Outlook To Improve Combination Strategies For The Immunotherapy Of Gbmmentioning
confidence: 99%
“…Therefore, improving delivery systems needs to be considered in order to increase delivery at the tumor site. In this regard, novel cyclic peptides modulating the BBB enhanced the brain delivery of mAbs [ 196 ]. Similarly, focused ultrasound-mediated BBB disruption improved anti-CD47 mAbs delivery to GBM tumors [ 199 ].…”
Section: Limitations Of Current Preclinical Models and Future Outlook To Improve Combination Strategies For The Immunotherapy Of Gbmmentioning
confidence: 99%
“…A drug molecule can normally pass through intercellular junctions (via the paracellular pathway). However, the tight junctions between two opposing cellular membranes limit this passage to small ions and hydrophilic molecules with a hydrodynamic radius <11 A [ 338 ] or between 400 and 500 Da [ 337 ], making protein transport difficult. Endocytic mechanisms that involve receptor mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) can facilitate the transport of some macromolecules and peptides across the BBB [ 339 ].…”
Section: Polypeptide Deliverymentioning
confidence: 99%
“…Any formulation that needs to cross the BBB requires a specific transporter for an active transport mechanism or an appropriate physicochemical property for passive diffusion [ 338 ]. Therefore, new technology-based approaches are needed, such as microparticles, functionalised nanocarriers, liposomes and chimeric peptide technology.…”
Section: Polypeptide Deliverymentioning
confidence: 99%
“…Linear and cyclic cadherin peptides as BBBM (e.g., HAV6, Ac-SHAVSS-NH2; ADTC5, Cyclo(1,7)Ac-CDTPPVC-NH2) have been shown to improve brain depositions of various sizes of proteins (e.g., 15 kDa lysozyme, 65 kDa albumin, 150 kDa IgG mAb) in C57BL/6 mice. [25][26][27] A combination HAV6 peptide and anticancer drug adenanthin has been shown to effectively suppress brain tumor growth and enhance animal survival in the mouse model of medulloblastoma brain tumor. 28 Recently, multiple treatments of experimental autoimmune encephalomyelitis (EAE) mice (an animal model of multiple sclerosis (MS)) with a combination of ADTC5 and BDNF significantly suppressed disease relapse compared to those treated with BDNF alone, ADTC5 alone, and PBS.…”
Section: Introduction and Epidemiologymentioning
confidence: 99%