Hydroxyapatite-poly(vinyl alcohol) core-shell nanoparticles for dual delivery of methotrexate and gemcitabine for bone cancer treatment

The delivery of multiple drugs with bone substitutes is the current strategy for the treatment of bone diseases. In this study, hydroxyapatite nanoparticles (HA NPs) as a core and poly(vinyl alcohol) (PVA) as the corona were developed for the dual delivery of anti-cancer drugs methotrexate (MTX) and gemcitabine (GEM). MTX was conjugated to PVA through ester linkages with a high payload of around 20%. GEM was then physically loaded onto the MTX conjugated-PVA-HA NPs with a loading efficiency of 83%. In vitro drug release studies of GEM-loaded-MTX conjugated-PVA-HA NPs in phosphate buffered saline (pH 7.4) showed a combined release of both MTX (25%) and GEM (60%) at the end of 10 days. Physically loaded MTX showed a burst release of around 50% compared to 16% by conjugated MTX within 24 h which supports the significance of conjugating drug molecules. Cell viability studies using osteosarcoma MG-63 cells confirmed that polymer grafted NPs were non-cytotoxic, while the drug-loaded NPs showed dose-dependent cytotoxicity. The synthesized NPs will be a promising bone-substitute material for the co-delivery of many therapeutic molecules for the treatment of bone diseases.