Optimization of a novel chelerythrine-loaded magnetic Fe3 O4 /chitosan alpha-ketoglutaric acid system and evaluation of its anti-tumour activities.

OBJECTIVES: A novel magnetic targeting anti-tumour drug delivery system (Fe3 O4 /KCTS-CHE) was designed using magnetic Fe3 O4 /chitosan alpha-ketoglutaric acid (Fe3 O4 /KCTS) as carrier and chelerythrine (CHE) as an anti-tumour drug model. Moreover, the anti-tumour activities and mechanisms of Fe3 O4 /KCTS-CHE were investigated.

METHODS: The preparation conditions of Fe3 O4 /KCTS-CHE microspheres were optimized by response surface methodology (RSM). The CHE drug release kinetics was evaluated by fitting the experimental data to standard release equations. The inhibitive activities of Fe3 O4 /KCTS-CHE microspheres against the HepG2 cells were estimated using MTT assay in vitro, and the mechanisms were studied using Hoechst 33258 staining.

KEY FINDINGS: The optimum preparation conditions were 11.68 : 1 for Fe3 O4 /KCTS:CHE ratio, 4 : 1 for oil/water ratio and 50.03 min for the ultrasonic time. The drug loading content and entrapment efficiency under the optimal conditions were 23.3% and 50.9%. The best fit was Higuchi model for the microspheres. The inhibitive rate on HepG2 cells of Fe3 O4 /KCTS-CHE nanoparticles varied from 30.19 ± 2.64% to 70.46 ± 6.42% at different concentrations from 50 to 400 mg/l in 72 h.

CONCLUSION: Fe3 O4 /KCTS-CHE exhibited effective anti-tumour activities against the HepG2 cells and induced cell apoptosis in HepG2 cells. Fe3 O4 /KCTS-CHE possess a high drug loading efficiency and entrapment efficiency, which are a new matrix for controlling release of drugs and a promising candidate for targeted drug delivery.