Research On Folic Acid-chitosan Modified 7-ethyl-10-HCPT Liposomes

7-ethyl-10-hydroxy camptothecin(SN-38)was the active metabolite of irinotecan(CPT-11),and CPT-11 is a kind of clinical antitumor medicine.SN-38 has high and strong activity,but some factors has limited its clinical application.The limitation include its poor water solubility,low oral bioavailability and fast body elimination.In this article,SN-38 liposomes(SN-38-LP)were prepared by super sonication and thin-film method.We synthesized a compound named FA-CS using folic acid and chitosan.Then through the charge effect,FA-CS was absorbed on the surface of SN-38-LP,and a new SN-38 liposomes(FA-CS-SN-38-LP)were prepared.The preparation can solve the problem of poor water solubility of SN-38.And we hope that FA-CS-SN-38-LP may target the tumor cell and release the drug slowly in the cell.Determined by single factor and orthogonal experiment,the prescription and technology of the liposomes were studied.We use the particle size,zeta potential,drug loadings,coating rate,the in vitro release and stability as the evaluation index,and the evaluation indexs were characterized.The average particle size of SN-38--LP and FA-CS-SN-38-LP is 158 nm and 239 nm respectively.The zeta potential of SN-38-LP is-7.15 mV,and the zeta potential of FA-CS-SN-38-LP is?18.63 m V.The entrapment effcienty of FA-CS-SN-38-LP was about 79.23%,and the drug loading percentage was about 3.85%.Dialysis method is used to study the in vitro release of the preparations.The result showed that the drug release of FA-CS--SN-38-LP was much slower comparaed with that of SN-38-Sol and SN-38-LP.The release curve of SN-38-LP and FA-CS-SN-38-LP are similar.MTT method was used to evaluated the in vitro cytotoxicity of three prepara--tions(SN-38-LP,FA-CS-SN--38-LP,SN-38-Sol),using tumor cells of MCF-7 and HepG-2.After incubation with drugs for 24 h,48 h and 72 h,the inhibition effect of FA-CS-SN-38-LP group was significantly better than that of SN-38-LP group and SN-38-Sol group.Cell inhibition degree is well relative to the concentration of the drug.Cell inhibitory effect on MCF-7 cells is better,and FA-CS-SN-38-LP showed a better inhibition effect on the MCF-7 cells compared with that of HepG-2 cells.S180 tumor-burdened mice model was established to evaluate the pharma--cokinetic and tissue distribution of FA-CS-SN-38-LP.In vivo antitumor activity of FA-CS-SN-38-LP was studed on S180 tumor-burdened model mice.We using weight inhibition rate and volume inhibition rate to evaluate the antitumor effect on mice.The results showed that the weight inhibition rate and volume inhibition rate of FA-CS-SN-38-LP group were 67.04% and 65.73% respectively.Compared with normal saline group,the tumor growth of SN-38-LP group and FA-CS-SN-38-LP group is slow,and the surface of the tumor did not fester or bleeding.Pathology examination was also done on tumor tissues.The picture showed that compared with normal saline group,tumor cells of FA-CS-SN-38-LP group decreased with different degrees of degeneration and arranged loosely.These results indicated that FA-CS-SN-38-LP maybe a good candicate to treat tumor disease.