Synthesis And Transfection Studies Of Lamellar Hydroxyapatite Drug Delivery Systems

Natural lamellar inorganic nano-materials and intercalative composites have gained widely attention in the field of gene delivery and composite materials,due to the unique two-dimensional lamellar structure and excellent mechanical properties.However,because of that natural lamellar inorganic nano-materials are not biodegradable,and therefore it has great significance to prepare a new type of two-dimensional lamellar nano-materials.The previous research has successfully synthesized lamellar HAp(LHAp)and magnetic lamellar HAp(mHAp)using template method,combining the excellent biocompatibility,bioactivity and biodegradability of HAp and the structure advantages of lamellar inorganic nano-materials,which is committed to expanding the application of HAp as drug and gene vectors.In this study,the anticancer drug 5-fluorouracil(5-FU)was successfully intercalated into the interlayer of LHAp and mHAp,as novel drug delivery vectors.The surfaces of LHAp and mHAp were modified by PEI,named PEI/LHAp/5-FU and PEI/mHAp/5-FU,which aimed to improve the surface zeta potentials.Then,PEI/LHAp/5-FU and PEI/mHAp/5-FU were respectively composited with DNA to study the transfection of drug carriers.The morphology and structure of LHAp/5-FU and mHAp/5-FU were characterized by transmission electron microscopy(TEM)and X-ray diffraction(XRD).The results indicated that LHAp/5-FU and mHAp/5-FU remained laminated structure and diffraction peaks moved left between 1~10°,which means the lamellar HAp was intercalated into 5-FU.FT-IR results revealed that the 5-FU molecules were successfully absorbed into LHAp and mHAp,and the ion-exchange with NO3ˉ occurred during the process.TGA confirmed that the drug loading capacity of mHAp was higher than that of LHAp.In vitro drug release indicated that LHAp/5-FU and mHAp/5-FU have good slow release performance.Rigter-Peppas model release kinetics results showed that release kinetics of LHAp/5-FU and mHAp/5-FU in the pH = 7.4 and pH = 1.2 were the coefficient of drug diffusion and carriers dissolution.Zeta potential results confirmed that PEI/LHAp/5-FU and PEI/mHAp/5-FU have the greatly higher zeta potentials than that of LHAp/5-FU and mHAp/5-FU,which is conductive to composite with DNA.The in vitro transfection result showed LHAp and mHAp possessed higher three-dimensional(3D)transfection efficiency compared with that of two-dimensional(2D).Due to the effect of magnetic targeting,the 2D and 3D transfection efficiency of mHAp were higher than those of LHAp,so magnetic targeting help to increase the transfection efficiency.