Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems
As less reactive <span style="font-variant: small-caps;">s</span>-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 <...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/12/6/1259 |
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| author | Iram Shahzadi Andrea Fürst Zeynep Burcu Akkus-Dagdeviren Shumaila Arshad Markus Kurpiers Barbara Matuszczak Andreas Bernkop-Schnürch |
| author_facet | Iram Shahzadi Andrea Fürst Zeynep Burcu Akkus-Dagdeviren Shumaila Arshad Markus Kurpiers Barbara Matuszczak Andreas Bernkop-Schnürch |
| author_sort | Iram Shahzadi |
| collection | DOAJ |
| description | As less reactive <span style="font-variant: small-caps;">s</span>-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 <span style="font-variant: small-caps;">s</span>-protected thiomer based on the less reactive substructure cysteine-<i>N</i>-acetyl cysteine (Cys-NAC) in order to obtain improved mucoadhesive properties. For this purpose, two types of <span style="font-variant: small-caps;">s</span>-protected thiomers, polyacrylic acid-cysteine-mercaptonicotinic acid (PAA-Cys-MNA) and polyacrylic acid-cysteine-<i>N</i>-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 <span style="font-variant: small-caps;">s</span>-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 <span style="font-variant: small-caps;">s</span>-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 <span style="font-variant: small-caps;">s</span>-protected thiomers exhibit higher mucoadhesive properties than highly reactive <span style="font-variant: small-caps;">s</span>-protected thiomers. |
| first_indexed | 2024-03-10T19:28:49Z |
| format | Article |
| id | doaj.art-8a15c4fa515d4ff7ad07b6ab41abfc77 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-10T19:28:49Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-8a15c4fa515d4ff7ad07b6ab41abfc772023-11-20T02:20:00ZengMDPI AGPolymers2073-43602020-05-01126125910.3390/polym12061259Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery SystemsIram Shahzadi0Andrea Fürst1Zeynep Burcu Akkus-Dagdeviren2Shumaila Arshad3Markus Kurpiers4Barbara Matuszczak5Andreas Bernkop-Schnürch6Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaCenter for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, AustriaAs less reactive <span style="font-variant: small-caps;">s</span>-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 <span style="font-variant: small-caps;">s</span>-protected thiomer based on the less reactive substructure cysteine-<i>N</i>-acetyl cysteine (Cys-NAC) in order to obtain improved mucoadhesive properties. For this purpose, two types of <span style="font-variant: small-caps;">s</span>-protected thiomers, polyacrylic acid-cysteine-mercaptonicotinic acid (PAA-Cys-MNA) and polyacrylic acid-cysteine-<i>N</i>-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 <span style="font-variant: small-caps;">s</span>-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 <span style="font-variant: small-caps;">s</span>-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 <span style="font-variant: small-caps;">s</span>-protected thiomers exhibit higher mucoadhesive properties than highly reactive <span style="font-variant: small-caps;">s</span>-protected thiomers.https://www.mdpi.com/2073-4360/12/6/1259less reactive thiomersmucoadhesionmucus diffusionpolyacrylic acid<span style="font-variant: small-caps">s</span>-protected thiomersthiolation |
| spellingShingle | Iram Shahzadi Andrea Fürst Zeynep Burcu Akkus-Dagdeviren Shumaila Arshad Markus Kurpiers Barbara Matuszczak Andreas Bernkop-Schnürch Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems Polymers less reactive thiomers mucoadhesion mucus diffusion polyacrylic acid <span style="font-variant: small-caps">s</span>-protected thiomers thiolation |
| 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 | less reactive thiomers mucoadhesion mucus diffusion polyacrylic acid <span style="font-variant: small-caps">s</span>-protected thiomers thiolation |
| url | https://www.mdpi.com/2073-4360/12/6/1259 |
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