Thermo-responsive hydrogels based on gelatin-alginate composition with humic acids intended for controlled drug delivery

Abstract The purpose of this work is to create a bioactive “smart” thermo-responsive hydrogel, which, when exposed to the body with a physiological temperature of 37°C, reversibly turns into a sol, which can be used to introduce drugs into hard-to-reach places, for local and long-term delivery of drugs, as well as for reducing doses of delivered drugs. Herein, we developed and studied hydrogel systems containing gelatin, sodium alginate and humic acids. All natural molecular polymers used are low cost and have non-toxic, biocompatible, biodegradable and non-immunogenic properties. In addition, using our own technology, humic acids with antioxidant, antibacterial and anti-inflammatory activity were obtained from lignite, which provided a concrete chance for the technological use of humic acids in accordance with the “waste-to-wealth” approach. Rheological studies confirmed that the hydrogel containing 14 %wt.gelatin and 6.4 %wt. sodium alginate is thermo-reponsive and has a gel-sol transition, manifested in a sharp decrease in its kinematic viscosity at a physiological temperature of 37°C. The FTIR spectra of the gelatin-sodium alginate-H 2 O and gelatin-sodium alginate-humic acids-H 2 O systems turned out to be similar. The small red and blue shifts in stretching and bending vibration positions occurred due to gelatin-sodium alginate, gelatin-humic acids and sodium alginate-humic acids interactions, and are similar to those observed in the literature, in particular due to a conformational change in the secondary structure of gelatin. The results of a study of the gel-sol transition time at a physiological temperature of 37°C for samples of the developed thermo-responsive bioactive gelatin-alginate hydrogel containing 6.4 %wt. sodium alginate and 14%wt. gelatin, as well as samples of this hydrogel modified with different contents of humic acids, visually showed a sharp increase in the transition time from 6 min to 11 min as a result of adding 2.5 %wt.humic acids. Thus, these studies showed that relatively small concentrations of humic acids can provide a prolonged drug delivery effect through the use of gelatin-sodium alginate hydrogel modified with humic acids on the surface of the human body.