Non-ionic thiolated cyclodextrins — the next generation
Ali Moghadam,1,2 Muhammad Ijaz,2,3 Mulazim Hussain Asim,2,4 Arshad Mahmood,2,5 Max Jelkmann,2 Barbara Matuszczak,6 Andreas Bernkop-Schnürch2 1Institute of Biotechnology, College of Agriculture, Shiraz University, Shiraz, Iran; 2Center for Chemistry and Biomedicine, Department of Pharmaceut...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-07-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/non-ionic-thiolated-cyclodextrins-the-next-generation-peer-reviewed-article-IJN |
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| author | Moghadam A Ijaz M Asim MH Mahmood A Jelkmann M Matuszczak B Bernkop-Schnürch A |
| author_facet | Moghadam A Ijaz M Asim MH Mahmood A Jelkmann M Matuszczak B Bernkop-Schnürch A |
| author_sort | Moghadam A |
| collection | DOAJ |
| description | Ali Moghadam,1,2 Muhammad Ijaz,2,3 Mulazim Hussain Asim,2,4 Arshad Mahmood,2,5 Max Jelkmann,2 Barbara Matuszczak,6 Andreas Bernkop-Schnürch2 1Institute of Biotechnology, College of Agriculture, Shiraz University, Shiraz, Iran; 2Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria; 3Department of Pharmacy, COMSATS Institute of Information and Technology, Lahore, Pakistan; 4Department of Pharmaceutics, Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan; 5Department of Pharmacy, COMSATS Institute of Information Technology Abbottabad, Pakistan; 6Center for Chemistry and Biomedicine, Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria 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-SH600 and β-CD-SH1200 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-SH600 and β-CD-SH1200 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. Keywords: thiolated cyclodextrin, mucosal delivery, inclusion complex |
| first_indexed | 2024-12-19T04:13:03Z |
| format | Article |
| id | doaj.art-6c59986368e347e0bfbe06a742506ad7 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-19T04:13:03Z |
| publishDate | 2018-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-6c59986368e347e0bfbe06a742506ad72022-12-21T20:36:22ZengDove Medical PressInternational Journal of Nanomedicine1178-20132018-07-01Volume 134003401339260Non-ionic thiolated cyclodextrins — the next generationMoghadam AIjaz MAsim MHMahmood AJelkmann MMatuszczak BBernkop-Schnürch AAli Moghadam,1,2 Muhammad Ijaz,2,3 Mulazim Hussain Asim,2,4 Arshad Mahmood,2,5 Max Jelkmann,2 Barbara Matuszczak,6 Andreas Bernkop-Schnürch2 1Institute of Biotechnology, College of Agriculture, Shiraz University, Shiraz, Iran; 2Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria; 3Department of Pharmacy, COMSATS Institute of Information and Technology, Lahore, Pakistan; 4Department of Pharmaceutics, Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan; 5Department of Pharmacy, COMSATS Institute of Information Technology Abbottabad, Pakistan; 6Center for Chemistry and Biomedicine, Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria 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-SH600 and β-CD-SH1200 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-SH600 and β-CD-SH1200 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. Keywords: thiolated cyclodextrin, mucosal delivery, inclusion complexhttps://www.dovepress.com/non-ionic-thiolated-cyclodextrins-the-next-generation-peer-reviewed-article-IJNThiolated cyclodextrinmucosal deliveryinclusion complex. |
| spellingShingle | Moghadam A Ijaz M Asim MH Mahmood A Jelkmann M Matuszczak B Bernkop-Schnürch A Non-ionic thiolated cyclodextrins — the next generation International Journal of Nanomedicine Thiolated cyclodextrin mucosal delivery inclusion complex. |
| 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 mdash the next generation |
| topic | Thiolated cyclodextrin mucosal delivery inclusion complex. |
| url | https://www.dovepress.com/non-ionic-thiolated-cyclodextrins-the-next-generation-peer-reviewed-article-IJN |
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