Evaluation of in vitro release of doxorubicin loaded in chitosan-alginate hydrogels

Polysaccharides are promising for responsive drug delivery under different stimuli, such as pH, ionic strength, and temperature, among others [1]. They can be classified as polyelectrolytes or non-polyelectrolytes, with the former being divided into cationic and anionic types. Chitosan (CH) and alginate (ALG) are polysaccharides widely used in hydrogel preparation, with CH being cationic and ALG anionic [2]. Through electrostatic interactions between amine groups (from CH) and carboxyl groups (from ALG), a biocompatible polyelectrolyte complex that is pH-responsive can be formed [3]. In this study, ALG/CH hydrogels were produced using factorial design by modifying synthesis parameters such as the ALG/CH ratio, pH, and speed of stirring, while evaluating the percentage of drug release of doxorubicin (DOX). The materials were characterized regarding their polymeric interactions, morphology, and swelling capacity at different pH levels. Additionally, the in vitro release of DOX was evaluated. Raman and FTIR spectroscopy results confirmed the characteristic modes of polysaccharides, indicating their interaction and the formation of ALG/CH hydrogels. Scanning electron microscopy (SEM) images revealed the porous structure of the samples in various formulations. Swelling tests indicated that hydrogel absorption increased in slightly acidic media. DOX release in an acidic environment increased with a higher CH proportion and was slower with a higher ALG content, confirming its pH responsiveness. Therefore, the obtained ALG/CH hydrogels have the potential to be biocompatible drug delivery systems.

References

[1] ALVAREZ-LORENZO, Carmen et al. Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery. Advanced drug delivery reviews, v. 65, n. 9, p. 1148-1171, 2013.

[2] GAO, Yang et al. Bifunctional alginate/chitosan stabilized perfluorohexane nanodroplets as smart vehicles for ultrasound and pH responsive delivery of anticancer agents. International Journal of Biological Macromolecules, v. 191, p. 1068-1078, 2021.

[3] KHAN, Yelena A. et al. Chitosan-alginate hydrogels for simultaneous and sustained releases of ciprofloxacin, amoxicillin and vancomycin for combination therapy. Journal of Drug Delivery Science and Technology, v. 61, p. 102126, 2021.