Evaluation of novel magnetic targeting microspheres loading adriamycin based on carboxymethyl chitosan

Abstract

Targeted drug delivery system delivers drug to diseased organ, tissue, or cells by utilizing some physical means and biological properties, such as pH gradients in the intestine, differences in capillary diameters, immune system, specific enzymatic degradation, receptor responses, and specific chemical environment at the site of the lesion. Combining two preparation techniques of magnetic microspheres and ion exchange, regarding the anticancer drug adriamycin (ADR) as a model drug, carboxymethyl chitosan (CMC) as carrier, and Fe3O4 ultrafine particles as magnetic material, novel drug-loaded magnetic microspheres-ADR loaded carboxymethyl chitosan magnetic microspheres (ADR-CMC-Mag-MS) were synthesized. In this study, cytotoxicity and in vivo pharmacokinetics of ADR-CMC-Mag-MS were evaluated. The 50% cell inhibiting concentration (IC50) value of ADR-CMC-Mag-MS was (0.051 ± 0.005) μg/mL. And the cytotoxicity against human hepatocellular (Hep3B) cells presented concentration dependence. The area under the curve (AUC) and the peak concentration (Cmax) of ADR-CMC-Mag-MS added magnetic field (mag field) were respectively (1061.68 ± 22.71) μg·min/mL and (6.18 ± 0.13) μg/mL, indicating that the prepared ADR-CMC-Mag-MS had good targeting ability. It was demonstrated that the novel microspheres could deliver the highly toxic anticancer drug to the target site, in order to maximize the drug efficacy and reduce the side effects under the action of the external magnetic field.