Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin.

摘要: Systemic chemotherapy has limited success in treating liver metastasis of colorectal cancer. Alternative approaches such as hepatic arterial infusion or trans chemoembolisation aim to deliver the locally address predominant disease. Chemoembolisation with drug eluting beads (DEB) designed at target over a protracted period time is new strategy reduce tumor burden metastases. To test this hypothesis, DEB possessing anionic groups capable ionically complexing cationic drugs were synthesised by suspension polymerisation method and fractionated produce an average size 75 μm. The loaded desired concentration either doxorubicin hydrochloride irinotecan prior administration immersion solution, yielding essentially 100% loading efficiency. determine their effect vivo, transplantable orthotopic isogenic rat model was used which based on intraportal injection 4 × 106 β-galactosidase transfected CC531 cancer cells into male WAG/Rij rats. By MTT assay, shown be sensitive both vitro IC50 being two orders magnitude lower for (110 nM after 72 h) compared (25 μM h). For vivo phase, differential expression ERK MAP kinase between cultured those inoculated noted using Western blotting techniques. This considered indicative passage-induced cell senescence that reduced sensitivity chemoembolisation. notwithstanding, single artery showed significant anticancer activity, measured reduction corresponding weight. Comparing agents, appears more advantageous because its activity excellent tolerability following dosages 20 30 mg/kg. Doxorubicin narrower window effective mg/kg but ineffective dose 2 We conclude agent may have potential patients metastasis, although appeared favourable safety profile.