Preparation Of Sorafenib Tosylate Nanoemulsion With X-ray Imaging

Hepatocellular carcinoma(HCC)is one of the most common malignancies and the third most deadly cancer in the world.Because the early symptoms of primary liver cancer are not obvious,it is difficult to be found.Most patients are in the late stage when they are diagnosed,and miss the best time for surgery.Most patients can only survive through drug treatment Sorafenib tosylate(SFT)is a multi-target tyrosine kinase inhibitor with dual inhibitory effects on tumor cell proliferation and angiogenesis.It is the first targeted drug approved by the U.S.Food and Drug Administration(FDA)for advanced HCC.However,SFT is insoluble in water,has low bioavailability,and has great toxic and side effects,so its clinical treatment effect is not ideal.Lipiodol is an organic iodine compound combining poppy seed oil and iodine.Because its density is higher or lower than that of the surrounding tissues of the human body and the X-ray transmission rate is different from that of the surrounding tissues,it is often used as contrast agent in clinic.However,Lipiodol is easy to cause vascular embolism and tissue necrosis during intravenous injection,and its application scope is very narrow.To address the above problems,Sorafenib tosylate-Lipiodol nanoemulsion(SFT-LIP NE)loaded is designed and tested in a series.The results showed that the prepared SFTLIP NE was spherical in appearance and uniformLy distributed,with an average particle size of about 158.10±2.62 nm,PDI of 0.12±0.01,Zeta potential of-23.70±0.10 mV,encapsulation rate of 85.4±0.75%,pH of 6.7.The tracer can be developed under CT.SFT-LIP NE can be stored statively for a long time and has good stability under simulated physiological conditions(incubation at 37℃ in high glucose DMEM containing 10%FBS for 72 h).SFT-LIP NE showed a good sustained release in vitro.The cumulative release of SFT was 91.38%within 72 h.SFT-LIP NE was significantly more lethal to tumor cells than SFT in vitro cytotoxicity assay and in vivo cytotoxicity assay.The results of oil red assay and fluorescence quantitative PCR of SFT related genes showed that SFT-LIP NE could significantly promote drug uptake by HCC cells.SFT-LIP NE was injected into mice through tail vein,tissue HE staining and hemolysis experiments,and the results showed that SFT-LIP NE has good biological safety.In conclusion,a series of experiments proved that compared with SFT alone,the prepared SFT-LIP NE can significantly inhibit the proliferation of tumor cells and promote the uptake of drugs by cells,thus achieving the dual effects of tracer and therapy.