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Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems

As less reactive s-protected thiomers can likely interpenetrate the mucus gel layer to a higher extent before getting immobilized via disulfide bond formation with mucins, it was the aim of this study to develop a novel type of s-protected thiomer based on the less reactive substructure cysteine-N-a...

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Autores principales: Shahzadi, Iram, Fürst, Andrea, Akkus-Dagdeviren, Zeynep Burcu, Arshad, Shumaila, Kurpiers, Markus, Matuszczak, Barbara, Bernkop-Schnürch, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362194/
https://www.ncbi.nlm.nih.gov/pubmed/32486313
http://dx.doi.org/10.3390/polym12061259
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author Shahzadi, Iram
Fürst, Andrea
Akkus-Dagdeviren, Zeynep Burcu
Arshad, Shumaila
Kurpiers, Markus
Matuszczak, Barbara
Bernkop-Schnürch, Andreas
author_facet Shahzadi, Iram
Fürst, Andrea
Akkus-Dagdeviren, Zeynep Burcu
Arshad, Shumaila
Kurpiers, Markus
Matuszczak, Barbara
Bernkop-Schnürch, Andreas
author_sort Shahzadi, Iram
collection PubMed
description As less reactive s-protected thiomers can likely interpenetrate the mucus gel layer to a higher extent before getting immobilized via disulfide bond formation with mucins, it was the aim of this study to develop a novel type of s-protected thiomer based on the less reactive substructure cysteine-N-acetyl cysteine (Cys-NAC) in order to obtain improved mucoadhesive properties. For this purpose, two types of s-protected thiomers, polyacrylic acid-cysteine-mercaptonicotinic acid (PAA-Cys-MNA) and polyacrylic acid-cysteine-N-acetyl cysteine (PAA-Cys-NAC), were synthesized and characterized by Fourier-transform infrared spectroscopy (FT-IR) and the quantification of attached disulfide ligands. The viscosity of both products was measured in the presence of NAC and mucus. Both thiomers were also evaluated regarding swelling behavior, tensile studies and retention time on the porcine intestinal mucosa. The FT-IR spectra confirmed the successful attachment of Cys-MNA and Cys-NAC ligands to PAA. The number of attached sulfhydryl groups was in the range of 660–683 µmol/g. The viscosity of both s-protected thiomers increased due to the addition of increasing amounts of NAC. The viscosity of the mucus increased in the presence of 1% PAA-Cys-MNA and PAA-Cys-NAC 5.6- and 10.9-fold, respectively, in comparison to only 1% PAA. Both s-protected thiomers showed higher water uptake than unmodified PAA. The maximum detachment force (MDF) and the total work of adhesion (TWA) increased in the case of PAA-Cys-MNA up to 1.4- and 1.6-fold and up to 2.4- and 2.8-fold in the case of PAA-Cys-NAC. The retention of PAA, PAA-Cys-MNA, and PAA-Cys-NAC on porcine intestinal mucosa was 25%, 49%, and 76% within 3 h, respectively. The results of this study provide evidence that less reactive s-protected thiomers exhibit higher mucoadhesive properties than highly reactive s-protected thiomers.
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spelling pubmed-73621942020-07-21 Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems Shahzadi, Iram Fürst, Andrea Akkus-Dagdeviren, Zeynep Burcu Arshad, Shumaila Kurpiers, Markus Matuszczak, Barbara Bernkop-Schnürch, Andreas Polymers (Basel) Article As less reactive s-protected thiomers can likely interpenetrate the mucus gel layer to a higher extent before getting immobilized via disulfide bond formation with mucins, it was the aim of this study to develop a novel type of s-protected thiomer based on the less reactive substructure cysteine-N-acetyl cysteine (Cys-NAC) in order to obtain improved mucoadhesive properties. For this purpose, two types of s-protected thiomers, polyacrylic acid-cysteine-mercaptonicotinic acid (PAA-Cys-MNA) and polyacrylic acid-cysteine-N-acetyl cysteine (PAA-Cys-NAC), were synthesized and characterized by Fourier-transform infrared spectroscopy (FT-IR) and the quantification of attached disulfide ligands. The viscosity of both products was measured in the presence of NAC and mucus. Both thiomers were also evaluated regarding swelling behavior, tensile studies and retention time on the porcine intestinal mucosa. The FT-IR spectra confirmed the successful attachment of Cys-MNA and Cys-NAC ligands to PAA. The number of attached sulfhydryl groups was in the range of 660–683 µmol/g. The viscosity of both s-protected thiomers increased due to the addition of increasing amounts of NAC. The viscosity of the mucus increased in the presence of 1% PAA-Cys-MNA and PAA-Cys-NAC 5.6- and 10.9-fold, respectively, in comparison to only 1% PAA. Both s-protected thiomers showed higher water uptake than unmodified PAA. The maximum detachment force (MDF) and the total work of adhesion (TWA) increased in the case of PAA-Cys-MNA up to 1.4- and 1.6-fold and up to 2.4- and 2.8-fold in the case of PAA-Cys-NAC. The retention of PAA, PAA-Cys-MNA, and PAA-Cys-NAC on porcine intestinal mucosa was 25%, 49%, and 76% within 3 h, respectively. The results of this study provide evidence that less reactive s-protected thiomers exhibit higher mucoadhesive properties than highly reactive s-protected thiomers. MDPI 2020-05-30 /pmc/articles/PMC7362194/ /pubmed/32486313 http://dx.doi.org/10.3390/polym12061259 Text en © 2020 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
Shahzadi, Iram
Fürst, Andrea
Akkus-Dagdeviren, Zeynep Burcu
Arshad, Shumaila
Kurpiers, Markus
Matuszczak, Barbara
Bernkop-Schnürch, Andreas
Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems
title Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems
title_full Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems
title_fullStr Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems
title_full_unstemmed Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems
title_short Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems
title_sort less reactive thiol ligands: key towards highly mucoadhesive drug delivery systems
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362194/
https://www.ncbi.nlm.nih.gov/pubmed/32486313
http://dx.doi.org/10.3390/polym12061259
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