Study On Oxaliplatin Long-circulating Thermosensitive Liposomes

As present, cancer still threaten the lives and the qualities of life of human beings seriously. Several anti-cancer agents are utilized limitedly in clinic because of the severe side effects. Liposome is one of the significant progresses in tumor treatment. Liposomal antineoplastic agents are characterized by targeting and delayed-releasing. Thus they can increase therapeutic index and effect and reduce toxicity. Long-circulating thermosensitive liposome is a new kind of liposome. When antineoplastic agents are encapsulated in liposome, not only the circulating time is prolonged but also the drug release is improved at the tumor site. As a result the therapeutic effect is improved.In this study, we selected the platinum anticancer agents Oxaliplatin as the model drug. The Oxaliplatin long-circulating thermosensitive liposomes (OLTL) were prepared and the quality was evaluated. Firstly, the HPLC method was established to determine the Oxaliplatin concentration. The formulation and prepare process were then studied. By the present thin film-freeze thawing method developed in this study, the encapsulation efficiency of water-soluble Oxaliplatin was improved about 50% with stable quality. The size and encapsulation efficiency of OLTL were under 200nm and above 90% respectively. The release behavior of the drug from liposomes was studied by dialysis method at 37℃and 41℃respectively. Most of the drug was released from the liposomes at 41℃in vitro.Pharmacokinetic study was carried out with SD rats. The results indicated the in vivo behavior of OLTL complied with the three compartment model. With the same dosage (18mg/kg) in rats by iv, the t_1/2α, t_1/2β K₁₀ and AUC of OLTL were 5.2, 3.2, 2.7 16.9 times those of Ox injection, moreover, the Vd and CL of the latter were 40.0 and 15.6 times those of the former. The tumor inhibition rate was evaluated with the established Lewis lung cancer model rats by iv. In vivo study revealed the tumor inhibition rate of OLTL was as high as 77.83% compared with that of the controlled groups.The adopted preparation technique was stable and repeatable with satisfactory results. It was demonstrated that OLTL not only prolonged the resident time of the drug in blood circulation, but also showed a higher anti-neoplastic activity compared with the controlled groups. The results indicated that OLTL could improve treatment efficacy effectively.