Study On Antitumor Effect Of Paclitaxel Nanoparticles Based On Clearing Macrophages

Purpose:With the increasing attention of the nano drug delivery system(NDDS),many problems have also been exposed.When the drug delivery system enters the body,it can easily be swallowed by the macrophages,resulting in that the drug can not effectively reach the lesion site.In order to overcome the characteristics of drug being easy to be phagocytosed in the process of metabolism,paclitaxel nanoparticles were prepared in this study,and then the characteristics of macrophages were removed by liposomes of cl-odronate sodium,to get rid of the fate easily cleared,to increase the drug concentration and increase Long cycle,enhance its bioavailability.Method:1)Paclitaxel(PTX)was used as a model drug,PLGA was used as a bulk material,and a modified W / O / W method was used to prepare PTX-PLGA nanoparticle.2)Preparation of sodium chlorophosphonate liposomes by rotary evaporation.3)The mice were used as the experimental model.The liposomes were injected into the caudal vein of mice at different time points(day1-day14)respectively.FACS analysis was performed by flow cytometry at different time points Mouse liver and spleen macrophages clearance.4)The effects of paclitaxel nanoparticles on plasma concentration and tissue distribution in mice were determined by HPLC after injection of sodium chlorophosphonate liposomes.5)Tumor mice were used as animal models to examine the antitumor effect of paclitaxel nanoparticles after injection of clodronic acid liposomes.And the detection of liver and kidney function.Result:1)Paclitaxel PLGA nanoparticles prepared by the method w / o / w can be prepared with better encapsulation efficiency of PTX-PLGA nanoparticles.2)Liposomes obtained from 86 mg of lecithin,8 mg of cholesterol,and 10 ml of chloroform gave the best efficiency of clearing liposomes from the efficiency of the prepared liposomes3)We made use of liposomes,the results show that by flow cytometry found that injection of sodium chlorophosphate liposomes,macrophages in the liver and spleen clearance was clear,the first day of the best removal effect.4)Pharmacokinetics and tissue distribution results show that,after the removal of macrophages,nanoparticles in the body to slow down the elimination rate,significantly extended half-life,less in the liver and spleen accumulation,more distribution in the blood,increased Long cycle5)Pharmacodynamics results show that,after the removal of macrophages,the nanoparticles showed a stronger anti-tumor effect,tumor size and weight was significantly reduced.Blood test indicators show: After the removal of macrophages,less drug accumulation in the liver,reducing the damage to the liver.Conclusion:The preparation of sodium CPL liposomes can clear the liver and spleen of macrophages can increase the bioavailability of paclitaxel as a model drug,problems have also been exposed.When the drug delivery system enters the body,it can easily be swallowed by the macrophages,resulting in that the drug can not effectively reach the lesion site.In order to overcome the characteristics of drug being easy to be phagocytosed in the process of metabolism,paclitaxel nanoparticles were prepared in this study,and then the characteristics of macrophages were removed by liposomes of clodronate sodium,to get rid of the fate easily cleared,to preparation of the nano-drug,the subject proposed to remove macrophages and reduce macrophages The characteristics of phagocytosis of nanoparticles to avoid the phagocytosis of the liver drugs to improve the half-life of the drug is conducive to play the characteristics of long circulation.