Magadiite-based dual-drug delivery system as well as its kinetic models of drug release and cytotoxicity

In order to reduce the cardiotoxicity induced by doxorubicin hydrochloride (Dox) during cancer treatment, a dual-drug delivery system based on magadiite for the cardioprotective agent carvedilol (CV) and the anticancer drug Dox (labeled as Mag-Dox/CV) was constructed through protonation, intercalation, and multi-step ion exchange. For the comparative study, a single-drug delivery system based on magadiite for Dox (labeled as Mag-Dox) was constructed by the same method. The loading capacity of Mag-Dox for Dox was about 30.0%; while the loading capacity of Mag-Dox/CV for Dox and CV were 15.64% and 32.87%, respectively. X-ray diffraction (XRD) patterns revealed that after protonation and intercalation of TBA+, the basal spacing of magadiite varied from 15.74 Å to 30.68 Å, indicating the successful intercalation of TBA⁺ into the interlayer of magadiite (labeled as Mag-TBA). Subsequently, after multi-step ion exchange between Mag-TBA and Dox solution, the basal spacing of the resulting Mag-Dox was 18.40 Å. While the Mag-TBA underwent multi-step ion exchange with the mixed solution of Dox and CV, the basal spacing of the resulting Mag-Dox/CV was 24.40 Å. Infrared spectroscopy confirmed that the TBA⁺ in Mag-TBA was completely replaced by drugs after multi-step ion exchanges. Drug release revealed that both Mag-Dox and Mag-Dox/CV showed sustained release of drugs in releasing medium. Moreover, they exhibited different kinetic models of drug release. Cytotoxicity experiments revealed that the Mag-Dox/CV exhibited much lower cytotoxicity towards H9C2 cells (rat cardiomyoblast cells) compared to Dox or Mag-Dox, while it maintains antitumor (HepG2 cells) activity at the same time, which was contributed by the dual-drug components of Dox and CV. All these results indicate that the magadiite may be a potential carrier for dual-drug delivery.