Mulazim Hussain Asim1, Ali Moghadam2, Muhammad Ijaz3, Arshad Mahmood4, Roman Xaver Götz5, Barbara Matuszczak6, Andreas Bernkop-Schnürch7. 1. Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Department of Pharmaceutics, Faculty of Pharmacy, University of Sargodha, 40100 Sargodha, Pakistan. 2. Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Institute of Biotechnology, College of Agriculture, Shiraz University, Shiraz, Iran. 3. Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, 54000 Lahore, Pakistan. 4. Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan. 5. Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. 6. Center for Chemistry and Biomedicine, Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. 7. Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
Abstract
AIM: The purpose of this study was to develop a novel mucoadhesive thiolated and S-protected gamma cyclodextrin (γ-CD) with an intact ring backbone to assure a prolonged residence time at specific target sites. METHOD: Thiolated γ-CD was generated through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. In the second step, thiol groups were protected by disulfide bond formation with 2-mercaptonicotinic acid (2-MNA). RESULT: Thiolated γ-CD displayed 1385 ± 84 µmol thiol groups per gram of oligomer and the amount of MNA determined in the S-protected oligomer was 1153 ± 41 µmol per gram of oligomer. In-vitro screening of mucoadhesive properties of thiolated and S-protected γ-CD was done by two methods. Rheological investigation revealed the conjugates non-mucolytic with only a slight increase in viscosity of thiolated and S-protected γ-CD as compared to unmodified γ-CD, whereas mucoadhesive properties of the new thiolated and S-protected γ-CD performed on freshly excised porcine intestinal mucosa showed 44.4- and 50.9-fold improvement in mucoadhesion, respectively. The new conjugates did not show any cytotoxicity to Caco-2 cells even at a concentration of 1% (m/v) for 24 h. In addition, in-vitro studies of α-amylase degradation of γ-CD, γ-CD-SH and γ-CD-SS-MNA confirmed that all conjugates are biodegradable. CONCLUSION: These outcomes predict that these new conjugates of γ-CD might provide a new favorable tool for drug delivery providing a prolonged residence time on mucosal surfaces.
AIM: The purpose of this study was to develop a novel mucoadhesive thiolated and S-protected gamma cyclodextrin (γ-CD) with an intact ring backbone to assure a prolonged residence time at specific target sites. METHOD: Thiolated γ-CD was generated through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. In the second step, thiol groups were protected by disulfide bond formation with 2-mercaptonicotinic acid (2-MNA). RESULT: Thiolated γ-CD displayed 1385 ± 84 µmol thiol groups per gram of oligomer and the amount of MNA determined in the S-protected oligomer was 1153 ± 41 µmol per gram of oligomer. In-vitro screening of mucoadhesive properties of thiolated and S-protected γ-CD was done by two methods. Rheological investigation revealed the conjugates non-mucolytic with only a slight increase in viscosity of thiolated and S-protected γ-CD as compared to unmodified γ-CD, whereas mucoadhesive properties of the new thiolated and S-protected γ-CD performed on freshly excised porcine intestinal mucosa showed 44.4- and 50.9-fold improvement in mucoadhesion, respectively. The new conjugates did not show any cytotoxicity to Caco-2 cells even at a concentration of 1% (m/v) for 24 h. In addition, in-vitro studies of α-amylase degradation of γ-CD, γ-CD-SH and γ-CD-SS-MNA confirmed that all conjugates are biodegradable. CONCLUSION: These outcomes predict that these new conjugates of γ-CD might provide a new favorable tool for drug delivery providing a prolonged residence time on mucosal surfaces.
Authors: Brunella Grassiri; Patrick Knoll; Angela Fabiano; Anna Maria Piras; Ylenia Zambito; Andreas Bernkop-Schnürch Journal: Int J Mol Sci Date: 2022-02-26 Impact factor: 5.923
Authors: Waleed Y Rizg; N Raghavendra Naveen; Mallesh Kurakula; Awaji Y Safhi; Samar S Murshid; Rayan Y Mushtaq; Walaa A Abualsunun; Majed Alharbi; Rana B Bakhaidar; Alshaimaa M Almehmady; Ahmad Salawi; Adel Al Fatease; Khaled M Hosny Journal: Pharmaceuticals (Basel) Date: 2022-04-18