An injectable kappa-carrageenan/konjac-glucomannan microgel platform for localized and controlled release of...

Polysaccharide-based physical hydrogels are promising drug-delivery platforms due to their biocompatibility, tunable mechanical properties, and reversible crosslinking. However, bulk hydrogels may require in situ gelation for administration, while controlled release of nanoparticles larger than the hydrogel mesh remains challenging. This study aimed to develop an injectable konjac glucomannan (KGM)-kappa carrageenan (KCAR) microgels platform, based on a previously established bulk hydrogel system, for the sustained delivery of doxorubicin (Dox)-loaded liposomes and protein-containing biomimetic nanoparticles termed Tumorosomes (Tumoro). Microgels were fabricated using a mild-temperature water-in-oil batch-emulsion method compatible with protein-containing nanoparticles. Incorporation of liposomes or Tumoro did not significantly affect microgel size or rheological properties. All formulations exhibited solid-like behavior at low strain, shear-thinning, and rapid structural recovery after high strain, supporting injectability. The reversible KGM-KCAR network enabled complete nanoparticle release within 48 h under physiological conditions. Empty microgels did not reduce 4 T1 cell viability, whereas Dox-loaded nanoparticles released from the microgels retained cytotoxic activity. Tumoro-loaded microgels produced a greater reduction in cell viability than dispersed Tumoro after 24 h, consistent with sustained release and enhanced Tumoro-cell association. These findings establish KGM-KCAR microgels as a preformed injectable platform with potential for localized and sustained delivery of protein-containing biomimetic nanoparticles in cancer therapy.