Layered Double Hydroxide Modified By PEGylated Hyaluronic Acid As A Hybrid Nanocarrier For Targeted Drug Delivery

In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU) as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU) was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG, synthesized by amidation method) on the surface of layered double hydroxide(LDH, prepared via hydrothermal method) and intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. LDH/HA-PEG/5-FU showed ideal drug release behaviors in in vitro drug release. Throughout MTT method, the drug carrier LDH/HA-PEG performed fine biocompatibility and the drug delivery system LDH/HA-PEG/5-FU showed more efficient endocytosis compared with LDH in vitro by Fluorescence Inversion Microscope System and Flow Cytometry testing.Besides, utilizing silane coupling agent, we grafted isocyanate group on the surface of LDH and then the drug gemcitabine and PEG get grafted so as to obtain functional organic-inorganic hybird drug delivery system LDH-Gemci-PEG. For the drug delivery system LDH-Gemci-PEG, we conducted a series of property characterization including FT-IR, XRD, laser particle size analyzer, TEM and Gel electrophoresis experiment which proved the successful grafting of Gemci and PEG. The drug-loading amount of Gemci was 2.99% through ultraviolet spectrophotometry. Then we successfully intercalated siRNA into LDH-Gemci-PEG's interlamination which showed its capability of loading siRNA. This phenomenon indicated that LDH could realize co-loading of both drug and siRNA.