Biomedical / LDHs Nanometer Explore New Methods For Preparing Composite Materials

In recent years, layered double hydroxides (layered double hydroxides, LDHs for short) is becoming a new drug carrier with great application prospect due to its good biocompatibility, low toxicity, tunability of the layer spacing and exchangeability of interlayer anionic. Methotrexate (MTX for short) is a common anticancer drug used in clinical therapy, and its serious side-effect, short plasma half-life and high efflux rate of MTX heavily restricted its application. In this paper, we choose MTX as the guest molecule and Mg-Al-LDHs as host material to synthesize MTX/LDHs intercalation compounds using different methods. On one hand, the synthesization of MTX/LDHs shows great antitumor effect of MTX because of the release properties of LDHs, and on the other hand, it greatly reduces the side-effect of MTX. The details are summarized as following:1. MTX/LDHs intercalation compounds with different particle sizes were prepared by controlling the dropping speed of precipitator and hydrothermal treatment time, by the improved coprecipitation method in alcohol-water solvent and NH3H2O as precipitator and the influence of particle size and the angle of inclination of MTX anion in LDHs interlayer on drug-loading and controlled release properties was also studied. The results show that MTX/LDHs has the highest crystallinity and the largest particle size when the dropping speed of precipitator is0.1mL/s. When the angles of inclination keep almost constant, the smaller nanoparticles have the longer release time than those of the larger ones; and when the particles’size keep almost constant, the particles with lager angles have the longer release time than those of the small ones.2. A novel method, mechanochemical-hydrothermal method was first used to synthesize MTX/LDHs. First, the optimum experimental conditions:NaOH amount:1.1mL (10.5mol/L), grinding time:60min, treatment temperature:100℃, treatment time:24h were obtained using orthogonal design. The products prepared by this new method were compared with that obtained by traditional coprecipitation method and the results indicate that the formal particles have more regular morphology and smaller particle size, and the release property is better than the latter product. And the influence of molar ratio of reactants (the molar ratio of Mg2+/Al3+/MTX) on the properties of products was investigated, and the obtained optimum ratio is2:1:0.5. Finally, the effects of different surfactants and surfactant concentration on the morphology of MTX/LDHs were studied.3. MTX/LDHs intercalation compounds with regular morphology, uniform particle size and good monodisperse 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 reaction temperature,ω(the molar ratio of water to surfactant Triton X-100) and reactant concentration on the morphology and the size of the products were systematically studied. The results show that low reaction temperature (40℃) is benefit to synthesize the particles with regular morphology and uniform particle size. And the particle size is directly related to the ω value and the concentration of MTX, when ω value is larger and the concentration of MTX is smaller, the diameter of the particle is larger. The prepared samples exhibited good sustained release properties and parabolic-diffusion model can better describe their release mechanism.