Preparation And Characterization Of PH-responsive Liposome Targeting Carrier

At present,drug chemotherapy is the main method used in clinical treatment of cancer disease,but due to the poor water solubility and other characteristics of low bioavailability of most anti-cancer drugs,the drug delivery system came into being.With the use of liposomes as a carrier,the bioavailability of the drug can be significantly improved,the side effects decreased and the drug targeting increased.Liposomes can only be produced in batches due to the complexity of the production process,resulting the high price of the liposome formulation.In this paper,the continuous production of liposomes was achieved by using the high-gravity equipment technology which could strengthen the mass transfer,and the preparation conditions were optimized by orthogonal experiment.The effect of resveratrol on the storage stability was studied,and the liposomes were modified.It can be used for targeted administration and provides new ideas for the preparation of smart liposomes.The main research contents and innovations of this paper are as follows:(1)With sorafenib as a model drug,the orthogonal experiment was used to optimize the conditions of preparation of liposomes in high-gravity rotating bed.It was found that the super-gravity level was 200,the oil-water feed ratio was 1:10,the operating temperature was 30 ?,The ratio of 1:7.5 to sorafenib was 1:20,and the average encapsulation efficiency of sorafenib was about 89%.Liposomes can significantly increase the dissolution of sorafenib in vitro,elute 80%in 10 h,and 100%at 48 h.Under the same conditions,the dissolution rate of the drug is only 4%at 10 h and 8%at 48 h.(2)Resveratrol,a different proportion of antioxidants,was added to study the effects of liposomal stability and antitumor properties in vitro.Adding 4%resveratrol,can significantly improve the stability of liposomes,at room temperature 25 ? and 4 ? conditions,placed 60 days after the addition of resveratrol did not add the degree of lipid oxidation and particle size changes Large,the drug leakage rate of up to 40%,while in the liposome by adding 4%resveratrol,the degree of oxidation and particle size almost no significant changes in drug leakage rate of less than 20%;in vitro anti-tumor experiments,Resveratrol enhanced the inhibitory effect of sorafenib on HepG-2 cells,and the IC50 of sorafenib decreased from 12.2 ?g/mL to 11.3 ?g/mL.(3)The synthesis 90%grafting rate lectin of the Eudragit S100-lectin,and its coating on the surface of liposomes.In vitro dissolution effects of sorafenib at different pH conditions:less than 40%of sorafenib was eluted from the foliage coated with ursi at pH 1.2 and 6.8,and pH 7.4,the drug was almost completely eluted,indicating that Utech can protect the liposomes from being acidified and the coated liposomes can be used for oral administration.