Study On Controlled Drug Release From Thermal-sensitive Cerasomes Using High Intensity Focused Ultrasound

In recent years, cerasome, as a new type of organic-inorganic nano-hybridmaterial has been developed as a drug carrier. It is a kind of biomimic materialderived from alkoxysilane hybrid lipid and can form a bilayer membranestructure like liposome with the surface covered with a layer of inorganic silicaframework. This unique structure makes the cerasome stable than conventionalliposome. While compared with the silica nanoparticles, cerasome has lowerrigidity and density due to its bilayer membrane structure. Therefore, cerasome isan ideal drug carrier which combines the advantages of liposome and silicananoparticles and meanwhile overcome the disadvantages of them.However, the stability of cerasome could make the drug release rate tooslow, and thus cannot maintain effective drug concentration of treatment in thetarget location, leading to drug resistance of tumor. In order to overcome theproblem, by incorporating thermosensitive lipids and lipids with a poly (ethyleneglycol)(PEG) moiety into the cerasomes, we developed a novel drug carrierwhich has high stability and can respond to high intensity focused ultrasound(HIFU)–“thermal-sensitive cerasome”. This thermal-sensitive carrier can makeuse of energy provided by high intensity focused ultrasound to open shell,releasing the embedding drug fast.In this paper, thermal-sensitive cerasomes with good stability andresponsive ability to HIFU were prepared successfully via a thin-film hydrationmethod in combination of sol-gel method and self-assembly process from lipids.Thermal-sensitive cerasome contains four lipid compositions including CFL,DPPC, MSPC and DPPE-PEG2000, with diameter about200nm and drugencapsulation efficiency reaching58.73±3.2%. In cell experiment, variousconcentrations of thermal-sensitive cerasome incubates with human umbilicalvein endothelial cells and mice’s bone marrow dendritic cells and T cells,respectively, and the results show that thermal-sensitive cerasomes are with lowcytotoxicity and immune toxicity. In vitro and in vivo HIFU controlled drugdelivery experiments show that thermal-sensitive cerasomes have goodcharacteristics of HIFU response.To sum up, thermal-sensitive cerasome prepared in this researching work isa novel drug carrier with high stability, good biocompatibility and propertyresponding to HIFU exposure, and will have an outstanding application prospectin the field of drug controlled release.