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Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue
The first objective was to investigate the transdermal iontophoresis of interferon beta 1b (IFN); the second was to determine whether the addition of 10 Arg residues at the N-terminus, creating a highly charged poly-Arg analogue (Arg(10)-IFN), increased delivery. Cumulative permeation of IFN and Arg...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358383/ https://www.ncbi.nlm.nih.gov/pubmed/32685921 http://dx.doi.org/10.1016/j.ijpx.2020.100051 |
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author | Dubey, S. Perozzo, R. Scapozza, L. Kalia, Y.N. |
author_facet | Dubey, S. Perozzo, R. Scapozza, L. Kalia, Y.N. |
author_sort | Dubey, S. |
collection | PubMed |
description | The first objective was to investigate the transdermal iontophoresis of interferon beta 1b (IFN); the second was to determine whether the addition of 10 Arg residues at the N-terminus, creating a highly charged poly-Arg analogue (Arg(10)-IFN), increased delivery. Cumulative permeation of IFN and Arg(10)-IFN after iontophoresis at 0.5 mA/cm(2) for 8 h was 6.97 ± 4.82 and 9.55 ± 1.63 ng/cm(2), respectively – i.e. >1000-fold less than that of ribonuclease A, cytochrome c and human basic fibroblast growth factor. Co-iontophoresis of acetaminophen showed that, in contrast to lysozyme, neither IFN nor Arg(10)-IFN interacted with skin to decrease convective solvent flow. Furthermore, there was no statistically significant difference between (i) iontophoretic delivery of IFN across intact or laser porated skin and (ii) passive or iontophoretic delivery of IFN across laser porated skin. Chromatographic characterisation supported the hypothesis that IFN was bound strongly to albumin. The formation of a ~ 86 kDa complex with albumin was probably responsible for the poor cutaneous delivery of IFN/Arg(10)-IFN despite the use of iontophoresis and/or laser microporation. Biopharmaceuticals might interact with specific proteins during iontophoretic transport and so decrease their (per)cutaneous delivery without affecting electroosmotic solvent flow, which is usually considered as a reliable marker to report on permeant binding during electrotransport across the skin. |
format | Online Article Text |
id | pubmed-7358383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-73583832020-07-17 Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue Dubey, S. Perozzo, R. Scapozza, L. Kalia, Y.N. Int J Pharm X Research Paper The first objective was to investigate the transdermal iontophoresis of interferon beta 1b (IFN); the second was to determine whether the addition of 10 Arg residues at the N-terminus, creating a highly charged poly-Arg analogue (Arg(10)-IFN), increased delivery. Cumulative permeation of IFN and Arg(10)-IFN after iontophoresis at 0.5 mA/cm(2) for 8 h was 6.97 ± 4.82 and 9.55 ± 1.63 ng/cm(2), respectively – i.e. >1000-fold less than that of ribonuclease A, cytochrome c and human basic fibroblast growth factor. Co-iontophoresis of acetaminophen showed that, in contrast to lysozyme, neither IFN nor Arg(10)-IFN interacted with skin to decrease convective solvent flow. Furthermore, there was no statistically significant difference between (i) iontophoretic delivery of IFN across intact or laser porated skin and (ii) passive or iontophoretic delivery of IFN across laser porated skin. Chromatographic characterisation supported the hypothesis that IFN was bound strongly to albumin. The formation of a ~ 86 kDa complex with albumin was probably responsible for the poor cutaneous delivery of IFN/Arg(10)-IFN despite the use of iontophoresis and/or laser microporation. Biopharmaceuticals might interact with specific proteins during iontophoretic transport and so decrease their (per)cutaneous delivery without affecting electroosmotic solvent flow, which is usually considered as a reliable marker to report on permeant binding during electrotransport across the skin. Elsevier 2020-07-08 /pmc/articles/PMC7358383/ /pubmed/32685921 http://dx.doi.org/10.1016/j.ijpx.2020.100051 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Dubey, S. Perozzo, R. Scapozza, L. Kalia, Y.N. Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue |
title | Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue |
title_full | Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue |
title_fullStr | Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue |
title_full_unstemmed | Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue |
title_short | Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue |
title_sort | specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1b and a poly-arg interferon beta-1b analogue |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358383/ https://www.ncbi.nlm.nih.gov/pubmed/32685921 http://dx.doi.org/10.1016/j.ijpx.2020.100051 |
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