Increased cytotoxicity of nanoparticle-carried Adriamycin in vitro and potentiation by verapamil and amiodarone.

The cytotoxicities of free cyanoacrylic nanoparticles, free Adriamycin, Adriamycin-loaded nanoparticles and a mixture of Adriamycin and nanoparticles are compared in cancer cell cultures. Increased cytotoxicity was observed in the sensitive (DC3F) subline when Adriamycin was in particulate form rather than free. In the derived pleiotropic resistant subline (DC3F AD/AZA), sensitivity to Adriamycin was completely restored with the conjugate. Addition of verapamil or amiodarone allowed an enhancement of efficiency of tenfold for free Adriamycin and between two- and fourfold for its conjugate form. Vectorization by nanoparticles and pharmacological modulation of cell membrane can act in synergy in synergy to overcome the resistance to Adriamycin in vitro.