Entirely S-protected thiolated hydroxyethylcellulose: Design of a dual cross-linking approach for hydrogels

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 181; pp. 292 - 299
• Main Authors: Fürst, Andrea, Shahzadi, Iram, Burcu Akkuş-Dağdeviren, Zeynep, Kali, Gergely, Hupfauf, Andrea, Gust, Ronald, Bernkop-Schnürch, Andreas
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2022
• Subjects: Cross-linking; Excipient; Polymer synthesis; Polymeric biomaterials; Rheology; Thiomers; Excipient; Polymeric biomaterials; Thiomers; Cross-linking; Rheology; Polymer synthesis
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2022.11.018

[Display omitted] The aim of this study was the synthesis and evaluation of entirely S-protected thiolated hydroxyethylcellulose (HEC) with low and high viscosity, as well as thiolated poly-L-lysine (poly-L-Lys) used as dual-acting ionic as well as thiol-disulfide exchange mediated cross-linking hydrogel. Bis(mercaptosuccinic acid) was covalently attached to low and high viscous HECs via Fisher esterification, obtaining S-protected polymers. Poly-L-Lys-cysteine was synthesized via amidation of poly-L-Lys-HBr with cysteine (Cys). Thiolated polymers were examined in terms of cytotoxicity and rheological behavior of hydrogels containing these thiomers was evaluated with a cone-plate rheometer. Thiomers showed less cytotoxicity compared to the corresponding unmodified polymers. Rheological studies showed that cross-linking occurred between the two polymers via thiol-disulfide exchange reactions facilitated by the complementary charges. Employing poly-L-Lys-Cys in a concentration of either 0.5 or 5% (m/v) resulted in a 34.5-fold or 17.3-fold as well as a 53.6-fold or 29.6-fold improvement in dynamic viscosity within 5 min at 37 °C on S-protected thiolated low and high viscous HEC, compared to the corresponding unmodified HECs, respectively. By the combination of anionic S-protected thiolated polymers with a cationic thiolated polymer, dual-acting hydrogels exhibiting a time dependent increase in viscosity can be designed.