Fabrication and evaluation of the zoledronic acid loaded cationic starch-hydroxyapatite-ZrO2 nanocomposites for bone disease treatment

초록

Addressing the challenge of low efficacy and systemic side effects of current bone disease therapies like zoledronic acid (Zol), we engineered novel core-shell nanocomposites (NCs) delivery system. This system features a core composed of bioactive hydroxyapatite (HA) and mechanically stable zirconia (ZrO<inf>2</inf>), coated with a cationic starch (CSt) shell (HA-ZrO<inf>2</inf>-CSt). Successful synthesis, CSt coating, and subsequent Zol loading were confirmed through comprehensive characterization, including characteristic shifts in zeta potential indicative of successful surface functionalization and drug incorporation, and high drug loading/entrapment efficiencies. Critically, the HA-ZrO<inf>2</inf>-CSt NCs demonstrated excellent in vitro cytocompatibility (>90 % MC3T3-E1 cell viability) and hemocompatibility (<5 % hemolysis), while significantly mitigating the vascular irritation observed with free Zol in an ex ovo CAM assay. Most importantly, the Zol-loaded NCs substantially enhanced osteogenic differentiation and matrix mineralization in vitro, increasing calcium deposition by 90.6 % compared to the differentiation control group, far exceeding the effect of unloaded NCs. This synergistic platform, combining an osteoinductive scaffold with controlled drug delivery that enhances therapeutic efficacy while reducing drug-associated toxicity, positions HA-ZrO<inf>2</inf>-CSt-Zol NCs as a highly promising multifunctional strategy for advancing bone regeneration therapies. © 2025 Elsevier B.V.

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