Study On The Targeting Liposomes Tethered With Biotin-ssDNA

ObjectiveTo study the feasibility of aptamer to be the targeted modifying of liposomes.Inspecting the binding characteristics between the cells and the Biotin-ssDNA-LP to evaluate the influence of Biotin-ssDNA to the binding specificity.And liposomes tethered with Biotin-ssDNA were prepared to study the effect on anti-tumor rate of the liposomes in vivo.MethodsFirst.examined the nature of drug Cabazitaxel before prescriptions,as well as established the method of determination of content and entrapment eff-iciency of Cabazitaxel liposomes by ultrafiltration-HPLC method,and thus laid the foundation for the subsequent process.Basing on the studies above,taking entrapment efficiency and the size of liposomes as the main indicators,investigated the formulation,process of preparation and freeze-drying of Cabazitaxel liposomes.Then,preparation the liposomes with FAM-6 instead of Cabazitaxel to investigate the targeting binding characteristics between cells and Cabazitaxel liposomes by FCM(flow cytometry)and fluorescence microscope,selecting the best quantity of Biotin-ssDNA in vitro.Furthermore,foundation the mice model of hepatic carcinoma to study the anti-tumor rate and the targeting of the liposomes.ResultsThe results of method validation indicated that the HPLC method was fit for the determination of content and entrapment efficiency of Cabazitaxel liposomes.After the investigation and optimization of the formulation and process of preparation of Cabazitaxel liposomes,and after the freeze-drying process,the entrapment efficiency was 93.18%,and the average particle size was 140nm,which achieved the desired objectives.The results of in vitro studies showed that the 5%Biotin-ssDNA versus to soybean lecithin molar mass was the best ratio,and from the results we can see the Biotin-ssDNA-LPs were targetability compaired with the ordinary liposomes.The data of in vivo study showed that the highest anti-tumor rate was the high-dose group of targeting liposomes and Cabazitaxel control group got good anti-tumor rate just lower than the high-dose group,the next was the mid-dose group and then was the low-dose group of targeting liposomes.The ordinary liposomes of Cabazitaxel got the lowest anti-tumor rate.When compared with Cabazitaxel control group the tumor inhibition rates all showing statistical difference(p<0.01).ConclusionAfter the studies in vitro and in vivo,we found that Biotin-ssDNA could improve the targeting and anti-tumor rate of liposomes.And Biotin-ssDNA could protect the non-targeted cells from the combinations with liposomes.It was feasibility that adapter to be targeted modifying of liposomes.