Preparation And Application Of Carboxymethyl Dextran-coated Magnetoliposomes

Abstract:Establishing multi-functional vesicles for the diagnosis and treatment of tumor is a long-term dream. Magnetoliposomes (MLs) are referred to as a hybrid of magnetic components and phospholipid assemblies. Because of integrating a variety of functional properties of liposomes and magnetic nanoparticles, such as biocompatibility, targeting, surface modification, controlled release, MRI, it would be a good carrier to achieve integration of diagnosis and treatment. However, it is still a big challenge to fabricate MLs along with colloidal stability, uniform nanosize, high encapsulation efficiency, good magnetic-responsiveness and with function of imaging.To solve the above problem, in this work, Fe3O4magnetic liposome decorated with carboxymethyl dextran(CMD) was prepared. And its application in nuclear magnetic resonance (NMR) imaging and controlled release was investigation, which laid a foundation for its application in the integration of diagnosis and treatment.Firstly, Fe3O4nanoparticle was synthesized by co-deposition method. The results showed that magnetic nanoparticles are superparamagnetic with diameter of3nm and a saturation magnetization of61.4emu/g.Then, CMD-MLs was synthesized by a thin lipid film hydration method, in which, phosphatidylcholine, amphiphilic CMD and cholesterol were the membrane materials, superparamagnetic Fe3O4nanoparticles (SPIONs) was magnetic components. The result showed the saturation magnetization of CMD-MLs was47.7emu/g and it had a narrow distribution with about120nm. At4℃, the CMD-MLs were very stable against more than one month storage. Besides, it was also stable in serum. And the relaxation efficiency (r2/r1) was57, it could be a good candidate as T2-weighted MRI contrast agent.Lastly, by remote loading method with an ammonium sulfate gradient, CMD-MLs-DOX was prepared. The encapsulation efficiency of DOX was higher than95%. The release rate and cumulative release would get faster and higher when the magnetic field intensity got stronger or the under time got longer. Meanwhile, the solubility of doxorubicin has pH dependence, at physiological pH(7.4), doxorubicin release rate was much slower than at acidic pH(5.0), which would lead to selectively release in tumor lesion area. MTT result revealed that CMD-MLs-DOX had good inhibition to SH-SY5Y cells.