Anticancer Efficacy Of Layered Double Hydroxides Loaded Sorafenib On A549 Non-small Cell Lung Cancer Cell Line

Objectives Sorafenib-Layered double hydroxides(S-LDHs)nano-preparation with good stability and controlled release of p H-sensitive drugs was be prepared,and be investigated the inhibitory effect of S-LDHs on lung cancer cell line A549 and drug distribution in vivo.Methods 1 S-LDHs nano-preparation was prepared by co-precipitation with sorafenib.2The size and morphology of S-LDHs nano-preparation were characterized using transmission electron microscopy(TEM)and photon correlation spectroscopy(PCS).3Drug release properties and drug loading capacity of S-LDHs nano-preparation were determined by ultraviolet spectrophotometry(UV)under neutral(p H7.4)environment and acidic(p H4.0)conditions.4 Cell inhibition experiment,confocal and Western Blot methods were used to investigate the inhibitory effect of S-LDHs nanometer materials on Non-Small Cell Lung Cancer cells.5 The effect of S-LDHs nano-preparation on metastasis and angiogenesis inhibition was investigated using wound-healing scratch and cell tubule formation assay.6 The serum and tissue concentration of S-LDHs nano-preparation was detected by high-performance liquid chromatography.Results 1 TEM showed that LDH nano-partical is a regular polygonal sheet and S-LDHs nano-preparation are irregular rods.For S-LDHs nano-preparation,the zeta potential was37.2 m V,with an average particle diameter of 224.1 nm,The particle size of 90 % S-LDHs nano-preparation is between 150-350 nm.2 The S-LDHs-loading capacity about 17%,stable in neutral(p H7.4)environment.Under acidic(p H4.0)conditions,self-disintegration of LDH and S is rapidly released.3 Experimental results showed that S-LDHs nanopreparation is more easily obtained by A549 cells and has more significant anti-cancer effects than S.Meanwhile,apoptosis rates of A549 cells were positively associated with the concentration of S-LDHs nano-preparation.4 In addition,S-LDHs nano-preparation can effectively inhibit the migration of A549 cells and the tubule-forming ability of human umbilical vein endothelial cell and is positively correlated with the concentration of SLDHs nano-preparation,compared with S.5 Compared with S,the results of HPLC showed that S-LDHs nano-preparation can have a higher plasma concentration and it is above 20 ?g/ml 24 h after administration.Under the protection of LDH,the distribution of S in all tissues in S-LDHs was markedly higher than that of the S group,especially in lung.Conclusions S-LDHs nano-preparation significantly improves the bioavailability of S,the anti-tumor effect is enhanced and the lung aggregation is higher than pure S,suggesting that S-LDHs nanometer can be used as potential cancer drugs for the targeted treatment of lung cancer.Figure24;Table6;Reference66...