Study Of Tegafur Complex Liposomes

Tegafur is a common drug for liver tumor with limited application because of strong adverse reaction,many complications and inferior targeting.Objective:To research common,long-circulating,long circulating thermosensitive,magnetic long circulating thermosensitive and controllable motion liposomes about their formulas,preparation technology,characters,targeting and pharmacokinetics regularity with liposome as a carrier,tegafur as a model drug and targets of liver targeting,low toxicity and delayed release.Methods:The enbedding ratio as an index was evaluated to the optimizing preparation technology with an orthogonal design.Tegafur common liposome was prepared with reverse phase evaporation and supersound method,and observed their freeze-drying condition.Tegafur long-circulating,long circulating thermosensitive and magnetic long circulating thermosensitive liposomes were prepared with the same method.Controllable moving liposome was prepared by linking a common liposome and a magnetic liposome with cholesterol-oligonucleotide.Their shapes,sizes,Zeta electric potential,magnetic propertied,crystal analysis etc.were detected with atomic force microscope,transmission electron microscope,nanosizer,X-ray diffracttometer, vibrate sample magnetometer,HPLC.Results:Materials in preparation,tissues and serum did not trouble the detection of tegafur in HPLC at 270nm.The optimal preparation parameters of Tegafur common liposome were 40 mg·ml^-1phospholipids,drug:phospholipids as 1:40,supersound for 6 min,phospholipids:cholesterol as 4:1 and with mean enbedding ratio as(68.64%±1.68)%.The mean size was 44.1nm for Blank liposome, 115.1nm for common liposome and 83.2nm for freeze-drying liposome.Zeta electric potential was-27.3±-7.50mv for common liposome and-32.3±-6.39mv for freeze-drying liposome.Accumulated release during 12 hours was＜10%for Tegafur long-circulating liposome with 123.9nm size.Tegafur long-circulating thermosensitive lipsome was with 67.71%embedding ratio,88.7nm size and 85.2% drug release as a peak when heating 30 min at 42℃.The size of magnetic nano-particle by improved co-precipitation was varied from 10 to 50nm by adjusting amount of hydrochloric acid and Polyglycol.The size reduction of ferroso-ferric oxide nano-particle was mainly due to reacting with hydrochloric acid.Tegafur magnetic long circulating thermosensitive liposome was with Zeta electric potential as -38.7±0.80mv and PH value as 7.42,saturation magnetization as about 36emu·g^-1with superparamagnetism and strong magnetism,embedding ratio as 65.48%,and which temperature increase value was positively correlated with its content and different current.AUC value of 8 hours at liver in Tegafur magnetic long circulating thermosensitive liposome group was 17.4 times of that of free drug group,and 3.9 times of that of Tegafur long-circulating liposome group.Its concentrations in serum and kidney were lower than those in free drug group.Its liver-targeted ratio was 73.9%.T_1/2(half-life)was longer in Tegafur long-circulating liposome group than free drug group.Controllable moving bi-liposome was 134.3 nm as general size,and with superparamagnetism,good magnetic response and strong magnetism.Conclusions:Tegafur complex liposome with a simple preparation condition and good stability could increase markedly the drug contribution in liver,decrease toxicity and increase drug availability.These prepared liposomes were reached objective in this research.