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Non-ionic thiolated cyclodextrins – the next generation

INTRODUCTION: The current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery. MATERIALS AND METHODS: Thiolated beta CD (β-CD) was prepared through bromine substitution of its hydroxyl groups followed b...

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Autores principales: Moghadam, Ali, Ijaz, Muhammad, Asim, Mulazim Hussain, Mahmood, Arshad, Jelkmann, Max, Matuszczak, Barbara, Bernkop-Schnürch, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045911/
https://www.ncbi.nlm.nih.gov/pubmed/30022823
http://dx.doi.org/10.2147/IJN.S153226
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author Moghadam, Ali
Ijaz, Muhammad
Asim, Mulazim Hussain
Mahmood, Arshad
Jelkmann, Max
Matuszczak, Barbara
Bernkop-Schnürch, Andreas
author_facet Moghadam, Ali
Ijaz, Muhammad
Asim, Mulazim Hussain
Mahmood, Arshad
Jelkmann, Max
Matuszczak, Barbara
Bernkop-Schnürch, Andreas
author_sort Moghadam, Ali
collection PubMed
description INTRODUCTION: The current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery. MATERIALS AND METHODS: Thiolated beta CD (β-CD) was prepared through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. The thiolated β-CD was characterized in vitro via dissolution studies, cytotoxicity studies, mucoadhesion studies on freshly excised porcine intestinal mucosa, and inclusion complex formation with miconazole nitrate. RESULTS: Thiolated β-CDs namely β-CD-SH(600) and β-CD-SH(1200) displayed 558.66 ± 78 and 1,163.45 ± 96 µmol thiol groups per gram of polymer, respectively. Stability constant (Kc) of 190 M(-1) confirmed the inclusion complex formation of miconazole nitrate with β-CD-SH. Inclusion complexes of β-CD-SH(600) and β-CD-SH(1200) resulted in 157- and 257-fold increased solubility of miconazole nitrate, respectively. In addition, more than 80% of thiol groups were stable even after 6 hours at pH 5. Both β-CD-SH compounds showed at least 1.3-fold improved solubility in water. In contrast to cationic thiolated CDs of the first generation, both thiomers showed no significant cytotoxicity. The mucoadhesive properties of the new thiolated CDs were 39.73- and 46.37-fold improved, respectively. CONCLUSION: These results indicate that β-CD-SH might provide a new favorable tool for delivery of poorly soluble drugs providing a prolonged residence time on mucosal surfaces.
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spelling pubmed-60459112018-07-18 Non-ionic thiolated cyclodextrins – the next generation Moghadam, Ali Ijaz, Muhammad Asim, Mulazim Hussain Mahmood, Arshad Jelkmann, Max Matuszczak, Barbara Bernkop-Schnürch, Andreas Int J Nanomedicine Original Research INTRODUCTION: The current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery. MATERIALS AND METHODS: Thiolated beta CD (β-CD) was prepared through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. The thiolated β-CD was characterized in vitro via dissolution studies, cytotoxicity studies, mucoadhesion studies on freshly excised porcine intestinal mucosa, and inclusion complex formation with miconazole nitrate. RESULTS: Thiolated β-CDs namely β-CD-SH(600) and β-CD-SH(1200) displayed 558.66 ± 78 and 1,163.45 ± 96 µmol thiol groups per gram of polymer, respectively. Stability constant (Kc) of 190 M(-1) confirmed the inclusion complex formation of miconazole nitrate with β-CD-SH. Inclusion complexes of β-CD-SH(600) and β-CD-SH(1200) resulted in 157- and 257-fold increased solubility of miconazole nitrate, respectively. In addition, more than 80% of thiol groups were stable even after 6 hours at pH 5. Both β-CD-SH compounds showed at least 1.3-fold improved solubility in water. In contrast to cationic thiolated CDs of the first generation, both thiomers showed no significant cytotoxicity. The mucoadhesive properties of the new thiolated CDs were 39.73- and 46.37-fold improved, respectively. CONCLUSION: These results indicate that β-CD-SH might provide a new favorable tool for delivery of poorly soluble drugs providing a prolonged residence time on mucosal surfaces. Dove Medical Press 2018-07-10 /pmc/articles/PMC6045911/ /pubmed/30022823 http://dx.doi.org/10.2147/IJN.S153226 Text en © 2018 Moghadam et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Moghadam, Ali
Ijaz, Muhammad
Asim, Mulazim Hussain
Mahmood, Arshad
Jelkmann, Max
Matuszczak, Barbara
Bernkop-Schnürch, Andreas
Non-ionic thiolated cyclodextrins – the next generation
title Non-ionic thiolated cyclodextrins – the next generation
title_full Non-ionic thiolated cyclodextrins – the next generation
title_fullStr Non-ionic thiolated cyclodextrins – the next generation
title_full_unstemmed Non-ionic thiolated cyclodextrins – the next generation
title_short Non-ionic thiolated cyclodextrins – the next generation
title_sort non-ionic thiolated cyclodextrins – the next generation
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045911/
https://www.ncbi.nlm.nih.gov/pubmed/30022823
http://dx.doi.org/10.2147/IJN.S153226
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