Synthesis and in vitro characterisation of preactivated thiolated gelatin

•A highly potent preactivated thiolated gelatin was synthesised with a coupling rate of 138 ± 15 μmol MNA per gram polymer.•Dynamic viscosity could be increase up to 400-fold and instantaneous gelation was observed.•Thermal stability increased with concentration and modification degree of gelatin.•The preactivated thiolated gelatin has highly mucoadhesive features with an increased maximal detachment force (MDF) as well as total work of adhesion (TWA) and a prolonged residence time on porcine mucosa of up to 5 days.

The aim of this study was to synthesise preactivated thiolated gelatin with potential mucoadhesive and cohesive properties.Gelatin from bovine skin (MW: approximately 50 kDa) was derivatised in two consecutive steps with iminothiolane followed by 2-mercaptonicotinic acid (MNA). The resulting preactivated thiolated gelatin (gelatin–TBA–MNA) was evaluated with respect to its physico-chemical properties such as isoelectric point (pI), viscosity, sol–gel transition and melting point and for its cytotoxicity. Muco-interactive features were investigated by tensile and rotating cylinder studies.Gelatin–TBA–MNA showed a preactivation rate of 138 ± 15 μmol MNA per gram polymer and a pI of 5.7 ± 0.3. The dynamic viscosity was increased up to 400-fold in comparison to unmodified control (p < 0.01 ∗ 10−5). In addition, gelatin–TBA–MNA displayed instantaneous gelation and an increase in melting point of up to 5 °C in comparison to control. According to cytotoxicity screening the novel gelatin derivative showed no toxic effect for up to 6 h. Total work of adhesion (TWA) of up to 71-fold (p < 0.01 ∗ 10−3) for gelatin–TBA–MNA in comparison to control was evident, as well as an up to 70-times extended residence time of the novel gelatin derivative on small intestinal porcine mucosa was recorded (p < 0.02 ∗ 10−9).Being highly mucoadhesive and showing excellent instantaneous gelling properties, the novel gelatin derivative might be a promising tool for the design of mucoadhesive drug delivery systems.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide