Ionic agarose derivatives as polyelectrolytic additives for drug release

Polysaccharides are being used as hydrogels for drug release in biomedical applications due to their inherent properties and biocompatibility. In this study, the synthesis, characterization, and application of ionic agarose derivatives are presented. Synthesis pathways for both anionic and cationic agarose derivatives with tunable degrees of substitution (DS) were established through homogeneous derivatization under mild conditions in ionic liquid. These derivatives partly retain their thermoreversible gelling behavior and can be used for polyelectrolyte systems. Agarose sulfates (AS) were synthesized in a one-step synthesis, while ammonium-bearing cationic agarose carbamates (AC) were synthesized via agarose phenylcarbonates (APC) with subsequent aminolysis. Both AS and AC were used in composite scaffolds of agarose and hydroxyapatite for sustained drug release into aqueous media. Layer-by-layer-coated alginate microbeads were prepared using oppositely charged agarose derivatives. Incorporating ionic agarose derivatives into these materials proved to effectively reduce the burst release and sustain the release of adenosine triphosphate (ATP), suramin, methylene blue, and A740003 over a time of 14 days. The release curves were evaluated using established models as well as two novel Langmuir-like models. Especially the latter two offered additional insight into the release and yielded higher scores in Akaike's Information Criterion rankings than commonly used models.