Research On Preparation And Pharmacokinetics For Oxaliplatin Long-circulating Liposomes

Oxaliplatin was now approved as first-line chemotherapy in combination with other antitumor drugs for the treatment of advanced colorectal cancer. And oxaliplatin was non-selective between normal and pathological tissue, and this posed a challenge regarding the strategy for treatment of tumors. Long-circulating liposomes are known to accumulate in tumours due to passive targeting through leaky endothelium of the tumour tissues.Objective:To prepare oxaliplatin long-circulating liposomes (PEG-liposomal L-oHP),and study its Pharmacokinetics. Methods:The best prescription and preparation of oxaliplatin long-circulating liposome was investigated by orthogonal design and investigate the influence of light and temperature to the appearance and the leakage of oxaliplatin long-circulating liposome,and also accelerate test through the encapsulation efficiency.High performance liquid chromatography (HPLC) was established to determine oxaliplatin concentration in plasma and organization homogenate.Results:The best prescription of oxaliplatin long-circulating liposome:The optimum prescription for the quality of the lecithin to cholesterol ratio of5:1,the amount of oxaliplatin1mg/ml,polyethylene glycol2000concentration of0.05%,the magnetic stirring speed of20r-min-1,the temperature of50℃,the injection speed of lml-min-1;Oxaliplatin long-circulating liposomes should be conserved under the temperature of4-8℃and keep away from air and light;The pharmacokinetics of the oxaliplatin long-circulating liposomes and the ordinary oxaliplatin liposomes were agreed to Two-Chamber Model.The AUC of oxaliplatin long-circulating liposomes was higher than that in ordinary oxaliplatin liposomes;In the targeting experiment, the MRT of long-circulating liposomes in heart, liver, spleen、 lung、 kidney、 intestine were respectively1.45、1.36、1.25、1.50、1.43、1.38times than those of ordinary oxaliplatin liposomes;and the AUC were4.22、3.02、1.89、2.78、2.12、2.73times.Conclusion:The oxaliplatin long-circulating liposomes had a longer blood residence time.