Study On Synthesis Of MTX / LDHs Nanocomposites And Its Antitumor Effect

Layered double hydroxides (LDHs) are the popular inorganic materials which have many advantages such as the positive layer charge, effective targeting, good bio-compatibility and easy bio-degradation. LDHs are composed of stacks of positively charged octahedral sheets and the exchangeable interlayer anions. It realizes controlled release of drugs by electrostatic interaction, space steric effect and hydrogen bond effect between layers and interlayer anions. As a common anticancer drug, methotrexate(MTX) often uses in clinical areas, but its serious side-effect, bad targeting and short plasma half-life restrict its application heavily. Here, we choose MTX as guest molecule, and Mg-Al-LDHs or Zn-Al-LDHs as layered carrier, to synthesize a series of MTX/LDHs nanocompounds by different methods. Then we systematically investigate the effect of the experiment conditions on morphology, drug-loading capacity and control-release properties of MTX/LDHs nanocompounds. Cytotoxicity tests on cancer cells of the MTX/LDHs nanocompounds are also carried. The details are summarized as following:1. MTX was intercalated into the LDHs via exfoliation-reassembly process to synthesize MTX/LDHs nanocompounds, the effect of reassembly time, different concentrations of MTX solutions and different solvents on the properties of MTX/LDHs nanocompounds had been researched carefully, then MTX/LDHs were determined by the cytotoxicity tests on cancer cells. The result shows the MTX/LDHs have higher crystallinity reassembled in MTX solution for 1 hour; it also find the MTX/LDHs synthesized in lower concentrations of MTX solutions present much better controlled-release property and effective anticancer effect than those from high concentrations. The MTX/LDHs reassembled in water show the best controlled-release property and effective anticancer effect, those reassembled in PEG-400/2.5% NH3H2O show irregular and even aggregated morphology, bad controlled-release property and effective anticancer effect.2. MTX/LDHs nanocompounds with sphere-like morphology were synthesized by reconstruction using carbon nanospheres as template. We systematically research the size of carbon nanospheres on the influence of morphology, drug-capacity, zeta potential and controlled-release property of MTX/LDHs, compared with the MTX/LDHs nanocompounds without the template. It indicates that those synthesized without the template show aggregated morphology, but those using carbon nanospheres as template exhibit sphere-like morphology. With the size of carbon nanospheres increased, the average particle size increases and morphology turns solid spheres into hollow spheres.3. MTX/LDHs compounds were synthesized in quaternary water/oil (W/O) reverse microemulsion solution containing Triton X-100, cyclohexane, n-butyl alcohol and aqueous solution. The influence of different conditions such as pH, ω, R and reactant temperature t on the morphology, drug-loading capacity and controlled-release property were systematically studied. The optimum experimental conditions to obtain regular morphology and high drug-loading capacity particles by orthogonal experiment are as follows:pH = 8.5, co=30, R=2:1:0.5 and t=40℃. The products prepared by this method in the optimum experimental conditions were tested and compared with MTX/LDHs obtained by co-precipitation method, ion exchange method and mechanochemical method. The result indicates that the pruducts prepared by reverse microemulsion method present higher drug-capacity and better anticancer effect than those obtained by other methods.