Polycarbonate Magnetic Microspheres Containing Tumor Necrosis Factor- α for Potential Targeted Hepatic Carcinoma Therapeutics

Abstract

Polycarbonate copolymers poly(trimethylene carbonate-co-5,5-dimethyl trimethylene carbonate) (PC, P(TMC-co-DTC)) was synthesized by the polymerization of trimethylene carbonate (TMC) and 5,5-dimethyl trimethylene carbonate (DTC) using Tin (II) 2-ethylhexanoate (Sn(Oct) 2 ) as a catalyst. The modified water-in-oil-in-water (w/o/w) solvent evaporation technique was adopted to produce anticancer magnetic polycarbonate microspheres TNF-PC-M containing human tumor necrosis factor-α (TNF) and Fe 3 O 4 magnetic ultrafine powders. The experiments evidenced that these magnetic polycarbonate microspheres had the strong magnetic responsiveness and high TNF loading concentration. Drug release studies showed that the microspheres sustained a steady release rate of TNF in PBS in vitro for up to 55 days. In vitro cytotoxicity assays demonstrated the microspheres had the high inhibition and anti-tumor action to human hepatocellular carcinoma (Bel-7204) cells in vitro. In vivo site-specific therapy in nude mice bearing Bel-7204 indicated that the microspheres possessed a markedly high antitumor activity.