Co-delivery of cisplatin and doxorubicin from calcium phosphate beads/matrix scaffolds for osteosarcoma therapy

- CaP beads/matrix composites for co-delivering of the cytostatics CDDP and DOX.
- DOX loaded matrix decreases and retard drug release compared to release from beads.
- DOX has a longer diffusion controlled release over 40 days compared to CDDP.
- Co-loaded composites synergistically enhance toxicity towards osteosarcoma cells.
- Long-term cytostatic release with synergistic effects while reducing drug quantity.

Bone substitute materials with a controlled drug release ability can fill cavities caused by the resection of bone tumours and thereby combat any leftover bone cancer cells. The combined release of different cytostatics seems to enhance their toxicity. In this study, calcium phosphate beads and matrix scaffolds are combined for a long-term co-delivery of cis-diamminedichloroplatinum (cisplatin, CDDP) and doxorubicin hydrochloride (DOX) as clinical relevant model drugs. Tricalcium phosphate/alginate beads as additional drug carrier are produced by droplet extrusion with ionotropic gelation and incorporated in scaffold matrix by freeze gelation without sintering. CDDP shows a short burst release while DOX has a continuous release measurable over the entire study period of 40 days. Drug release from matrix is decreased by ~ 30% compared to release from beads. Nevertheless, all formulations follow the Korsmeyer-Peppas release kinetic model and show Fickian diffusion. Cytotoxic activity was conducted on MG-63 osteosarcoma cells after 1, 4, and 7 days with WST-1 cell viability assay. Co-loaded composites enhance activity towards MG-63 cells up to ~ 75% toxicity while reducing the released drug quantity. The results suggest that co-loaded beads/matrix scaffolds are highly promising for osteosarcoma therapy due to synergistic effects over a long period of more than a month.

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