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WITHDRAWN: Specific protein-protein interactions limit the cutaneous iontophoretic transport of interferon beta-1B and a poly-ARG interferon beta-1B analogue
- Source :
- International Journal of Pharmaceutics: X, Vol 2, Iss, Pp 100051-(2020), International Journal of Pharmaceutics: X
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- 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 (Arg10-IFN), increased delivery. Cumulative permeation of IFN and Arg10-IFN after iontophoresis at 0.5 mA/cm2 for 8 h was 6.97 ± 4.82 and 9.55 ± 1.63 ng/cm2, 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 Arg10-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/Arg10-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.<br />Graphical abstract Unlabelled Image
- Subjects :
- Skin Absorption
Basic fibroblast growth factor
Pharmaceutical Science
lcsh:RS1-441
02 engineering and technology
Pharmacology
Administration, Cutaneous
030226 pharmacology & pharmacy
lcsh:Pharmacy and materia medica
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Humans
Ribonuclease
Skin
Transdermal
Iontophoresis
biology
Electromigration
Cytochrome c
Protein delivery
Protein interaction
Albumin
Interferon beta-1b
Transdermal iontophoresis
Interferon (IFN)
021001 nanoscience & nanotechnology
chemistry
biology.protein
Lysozyme
Electroosmosis
0210 nano-technology
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 25901567
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- International Journal of Pharmaceutics: X
- Accession number :
- edsair.doi.dedup.....ddc09036e3f0669d8e1c61722b534112