Polyelectrolyte Chondroitin Sulfate Microgels as a Carrier Material for Rosmarinic Acid and Their Antioxidant Ability

Polyelectrolyte microgels derived from natural sources such as chondroitin sulfate (CS) possess considerable interest as therapeutic carriers because of their ionic nature and controllable degradation capability in line with the extent of the used crosslinker for long-term drug delivery applications. In this study, chemically crosslinked CS microgels were synthesized in a single step and treated with an ammonia solution to attain polyelectrolyte CS^-[NH₄]⁺ microgels via a cation exchange reaction. The spherical and non-porous CS microgels were injectable and in the size range of a few hundred nanometers to tens of micrometers. The average size distribution of the CS microgels and their polyelectrolyte forms were not significantly affected by medium pH. It was determined that the -34 ± 4 mV zeta potential of the CS microgels was changed to -23 ± 3 mV for CS^- [NH₄]⁺ microgels with pH 7 medium. No important toxicity was determined on L929 fibroblast cells, with 76 ± 1% viability in the presence of 1000 μg/mL concentration of CS^-[NH₄]⁺ microgels. Furthermore, these microgels were used as a drug carrier material for rosmarinic acid (RA) active agent. The RA-loading capacity was about 2.5-fold increased for CS^-[R]⁺ microgels with 32.4 ± 5.1 μg/mg RA loading, and 23% of the loaded RA was sustainably release for a long-term period within 150 h in comparison to CS microgels. Moreover, RA-loaded CS^-[R]⁺ microgels exhibited great antioxidant activity, with 0.45 ± 0.02 μmol/g Trolox equivalent antioxidant capacity in comparison to no antioxidant properties for bare CS particles.