Preparation Of Several New Liposomes Of Oxaliplatin And Targeting, Pharmacokinetics For Colon Cancer

Oxaliplatin is a common drug for colon cancer with limited application because of strong adverse reaction,many complications and inferior targeting.Objective:To research common,long-circulating,long circulating thermosensitive, long circulating immunoliposomes about their formulas,preparation technology,characters,targeting and pharmacokinetics regularity with liposome as a carrier,Oxaliplatin as a model drug and target of colon targeting,low toxicity and delayed release.Methods:The enbedding ratio as an index was evaluated to the optimizing preparation technology with an orthogonal design.Oxaliplatin common liposome was prepared with reverse phase evaporation.Oxaliplatin long-circulating, long circulating thermosensitive and long circulating immunoliposomes were prepared with the same method.Their shapes,sizes,concents etc.were detected with nanosizer and HPLC.Results:Materials in preparation,tissues and serum did not trouble the detection of Oxaliplatin in HPLC at 250nm.The optimal preparation technology of Oxaliplatin common liposome was 40 mg·ml^-1 phospholipids,drug: phospholipids as 1:40,taking ultrasound for 6 min,phospholipids:cholesterol as 4:1 and with mean enbedding ratio as(85.46%±2.31%).The mean size was 69.4 nm for Blank liposome,79.3 nm for common liposome.Accumulated release during 12 hours was＜10%for Oxaliplatin long-circulating liposome with 108.1 nm size.Oxaliplatin long-circulating thermosensitive lipsome was with 85.24%embedding ratio,118.2 nm size and 89.4%drug release as a peak when heating 30 min at 42℃.Targeting efficiency of Oxaliplatin long circulating immunoliposome group with 57.3%(Te) was 1.3 times of that of Oxaliplatin long circulating thermosensetive liposome group, and 4.6 times of that of Oxaliplatin long-circulating liposome group.Its concentrations in serum,lung,kidney and heart were lower than those in free drug group.Conclusions:Oxaliplatin complex liposome was easy for industry,stabile well, could increase markedly the targeting in colon,decrease kidney toxicity and reached objective of this research.