In Vivo Study Of PH-sensitive Liposome

Objective:According to data released by the International Federation of cancer,the incidence of cancer in China accounts for almost half of the world,with an average of 6 per minute per day being diagnosed as a malignant tumor.At present,the anti-tumor drugs have the disadvantages of poor targeting,high toxicity and poor treatment effect.Liposome is a kind of similar in biofilm structure of double molecular layer of microcapsules,because of its similar cell structure into the human body is mainly the reticuloendothelial system phagocytic and for targeting drugs to gather in the liver,spleen and lung.But the liposome as drug carrier still has the disadvantages such as poor target to disease,poor stability and so on.Docetaxel(DTX)is a taxoid anticancer drugs,by interfering with cell with mitotic and interphase cells need to function of the microtubule network division and anti-tumor effects.The West he sico and free tubulin combined promote tubulin assembly into stable microtubules,and inhibit the depolymerization,lead to a loss of normal function of microtubules and microtubule fixed,thereby inhibiting cell mitosis,to prevent a large number of cancer cell division and guide cancer cells to die.Studies have already pointed out,the tumor cells to acidity environment,which is a marker of tumor tissue,the formation reasons and diseased tissue cell metabolism mechanism anomaly is closely related to.Based on the above,we designed a kind of acid sensitive liposome.The acid sensitive liposome mainly includes pH sensitive peptide(Low Insertion Peptides pHLIP,pH)and anti tumor drug DTX.By studying its in vivo activity,it provides the basis for clinical application.Methods:According to the literature and preliminary experiment,the liposome with film dispersion method was prepared,and the particle size,encapsulation efficiency and drug loading were also investigated.Did labeled liposomes were designed and constructed.The nude mice were tumor models,and the targeting of liposomes was evaluated by in vivo imaging technique.By comparing the targeted effects of different liposomes,the advantages of pHLIP modified liposomes in the targeting.The nude mice was picked as the animal model.we measured the weight after administration and the weight-time curve was drawed to evaluate the systemic toxicity of each group.At the same time,we used vernier caliper to measure the tumor cell,and the therapeutic effect was evaluated by tumor volume-time curve.Result:The average size of liposomes was 112.8nm,the encapsulation efficiency was 95.9%,the drug loading rate was 4.83%,and all the indexes were in line with the requirements.In the targeted experiments,the free Did could not target to the tumor site,although the normal liposome had a certain effect,but the effect was significantly lower,and the effect decreased with time.PHLIP modified liposome has a clear effect on the target,and it still has strong localization after 48 h,which indicates that it has good stability.In antitumor experiment,tumor volume of control group was significantly increased,the volume of the free DTX group is slightly variable.volume of common preparation group(NL)had no obvious change,and pHLIP modified liposomes group(PL)was decreased,it was indicated that the PL group has significant advantages on antitumor effects compared with other preparation.Each weight of nude mice in the experiment had no obvious change,it was proved that toxicity was low.Conclusions:pH sensitive liposomes modified by pHLIP have a advantage in the target and antitumor effect,and its toxicity was low.