Research On Preparation And Pharmacokinetics For Long-circulating β-elemene Liposomes

β-elemene is extracted from one of the traditional Chinese herbal medicine Wenchow Turmeric Rhizome,and has the treatment of cancer.PEG2000 is one kind of amphipathic macromolecule material,which could be used as protectant in liposomes and has the potential of prolonging resident time in vivo.In this study we intend to prepare the long-circulatingβ-elemene liposomes to reduce the adverse reaction and enhance the antitumor activity ofβ-elemene.The GC method was established to determine theβ-elemene concentration,and then it was used to dentermineβ-elemene quantity and entrapment efficiency accurately.To optimize the prescription and preparation of long-circulatingβ-elemene liposomes according to the entrapment efficiency,long-circulatingβ-elemene liposomes were prepared by the following methods:thin film vesicles method, reverse-phase evaporation vesicles method,ethanol injection method,diethyl ether injection method,and the ethanol injection method was the best method for the preparation of long-circulatingβ-elemene liposomes.A orthogonal test was carried out, and the best prescription was:The weight proportion of lecithin to cholesterol was 5:1,the weight ofβ-elemene was 50mg,0.05% PEG2000,Conclusion:The optimized formulation of PEG2000-complexed long-circulatingβ-elemene liposomes is reasonable in prescription,practicable in technology,and the envelope efficiency of long-circulatingβ-elemene liposomes was 92.7%.the diameter of long-circulatingβ-elemene liposomes was detected by laser particle analyzer,and morphological characteristic of long-circulatingβ-elemene liposomes was observed by transmission electron microscope.long-circulatingβ-elemene liposomes was kept in the low temperature-irradiance instrument at 4℃,4500Lx, the appearance and rate of percolation were observed at the 5th&10th day; liposome was kept at room temperature (25℃) and in the fridge (4～8℃),the appearance and rate of percolation were observed at the 1 month later; long-circulatingβ-elemene liposomes was kept at room temperature (25℃) and in the fridge (4～8℃),the appearance and rate of percolation were observed at the 1st, 2nd,3rd and 6th month,for the accelerated test.The results showed that long-circulatingβ-elemene liposomes should be conserved at a low temperature and keep away from air and light in order to ensure stability of long-circulatingβ-elemene liposomes.The pharmacokinetic parameters and tissues distribution of long-circulatingβ-elemene liposomes andβ-elemene liposomes injection were studied after intravenous injection long-circulatingβ-elemene liposomes orβ-elemene liposomes injection to rats.β-elemene concentration in plasma and tissues was determined by GC.Theα,T1/2β,K12 and AUC of long-circulatingβ-elemene liposomes groups were higher thanβ-elemene liposomes, and the T1/2α,Vc,CL,K10 of the latter were lower;long-circulatingβ-elemene liposomes were distributed mainly in liver,spleen, kidney,intestine,compared with theβ-elemene liposomes groups,the long-circulatingβ-elemene liposomes groups had larger area under the curve values in liver,spleen,lung,and the long-circulatingβ-elemene liposomes could reduce the accumulation in the heart, as a result, the cardiotoxic was reduced.