A hybrid drug delivery system coloaded with different drugs for synergistic drug delivery was developed. Alginate/calcium carbonate (CaCO3) hybrid microparticles (MPs) were fabricated via a facile coprecipitation method under mild conditions without using any organic solvent and surfactant. Due to the incorporation of negatively charged alginate chains onto the surface, the obtained hybrid MPs with spherical morphology showed good colloidal stability in an aqueous solution. An antitumor drug (doxorubicin, DOX) and a drug resistance reversal agent (verapamil, VP) were coloaded in the hybrid MPs simultaneously to obtain dual-drug-loaded MPs (DOX/VP/MP). Due to the presence of inorganic CaCO3 (∼54 wt%), the drugs could be loaded in the hybrid MPs with high encapsulation efficiency and the drug release could be effectively sustained. The cell growth inhibition of the drug-loaded MPs was evaluated in HeLa cells. An in vitro study showed DOX/VP/MP exhibited higher cell growth inhibition as compared with DOX monodrug-loaded MPs (DOX/MP). These results suggest the hybrid MPs can potentially be used as a synergistic drug delivery platform for cancer chemotherapy.

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