Abstract

The aim of this study was the design and evaluation of an entirely S-protected thiomer as matrix for intraorally administered films.

The highly bucco-adhesive gelatin thiomer was designed based on the ligand cysteamine which was connected via disulfide bond with the aromatic leaving group 2-mercaptopyrimidine-4,6-diol (2-MPD). The thiol ligand cysteamine 2-MPD (Cys-2-MPD) was synthesized via the coupling of dimerised 2-MPD to cysteamine (Cys) and then attached to gelatin scaffold via a carbodiimide mediated reaction. The entirely S-protected thiomer (gelatin-Cys-2-MPD) was characterized with respect to its thiolation efficiency, safety, melting point and mucoadhesive features. Thiomer films were prepared and assessed for in-vitro dislodgement stress via rotating cylinder and tensile studies on porcine buccal mucosa.

Gelatin-Cys-2-MPD showed a coupling rate of 392±41 μmol 2-MPD per gram polymer and provides 100% protection efficiency of total amount of attached sulfhydryl groups. The cytotoxic safety profile provided a survival rate of over 90% after 24 hours of incubation. Mucoadhesive features assessed via rheological investigations of mucus-polymer mixtures showed an up to 4-fold increased polymer mucus interaction in comparison to non-thiolated control (p<0.05∗10-4). In-vitro rotating cylinder studies recorded nearly 20-times extended residence time of entirely S-protected buccal films in comparison to non-thiolated control as well as up to 26-fold increased total work of adhesion (TWA) (p<0.04∗10-3) was evident for the thiomer.

Being highly bucco-adhesive, the novel designed entirely S-protected gelatin features highly mucoadhesive properties which are beneficial for intraorally applied films.

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