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Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides

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....

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Detalles Bibliográficos
Autores principales: Ulapane, Kavisha R., Kopec, Brian M., Siahaan, Teruna J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920923/
https://www.ncbi.nlm.nih.gov/pubmed/31683745
http://dx.doi.org/10.3390/pharmaceutics11110568
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author Ulapane, Kavisha R.
Kopec, Brian M.
Siahaan, Teruna J.
author_facet Ulapane, Kavisha R.
Kopec, Brian M.
Siahaan, Teruna J.
author_sort Ulapane, Kavisha R.
collection PubMed
description 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. Linear and N-to-C terminal cyclic ADTHAV peptides were designed by combining the sequences of ADTC5 and HAV6. These novel cyclic peptides were used to deliver an IRdye800CW-labeled IgG monoclonal antibody into the brain. Cyclic HAVN1 and HAVN2 peptides deliver IgG into the brain, while the parent linear HAV6 peptide does not. Cyclic and linear ADTHAV and ADTC5 peptides enhanced brain delivery of IgG mAb, in which cyclic ADTHAV peptide was better than linear ADTHAV (p = 0.07). Cyclic ADTHAV and ADTC5 influenced the distribution of IgG mAb in other organs while HAV6, HAVN1 and HAVN2 did not. In summary, the novel cyclic peptides are generally better BBB modulators than their linear counterparts for delivering IgG mAb into the brain.
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spelling pubmed-69209232019-12-24 Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides Ulapane, Kavisha R. Kopec, Brian M. Siahaan, Teruna J. Pharmaceutics Article 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. Linear and N-to-C terminal cyclic ADTHAV peptides were designed by combining the sequences of ADTC5 and HAV6. These novel cyclic peptides were used to deliver an IRdye800CW-labeled IgG monoclonal antibody into the brain. Cyclic HAVN1 and HAVN2 peptides deliver IgG into the brain, while the parent linear HAV6 peptide does not. Cyclic and linear ADTHAV and ADTC5 peptides enhanced brain delivery of IgG mAb, in which cyclic ADTHAV peptide was better than linear ADTHAV (p = 0.07). Cyclic ADTHAV and ADTC5 influenced the distribution of IgG mAb in other organs while HAV6, HAVN1 and HAVN2 did not. In summary, the novel cyclic peptides are generally better BBB modulators than their linear counterparts for delivering IgG mAb into the brain. MDPI 2019-10-31 /pmc/articles/PMC6920923/ /pubmed/31683745 http://dx.doi.org/10.3390/pharmaceutics11110568 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ulapane, Kavisha R.
Kopec, Brian M.
Siahaan, Teruna J.
Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides
title Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides
title_full Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides
title_fullStr Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides
title_full_unstemmed Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides
title_short Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides
title_sort improving in vivo brain delivery of monoclonal antibody using novel cyclic peptides
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920923/
https://www.ncbi.nlm.nih.gov/pubmed/31683745
http://dx.doi.org/10.3390/pharmaceutics11110568
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