Preparation And Bioavailability Of Anticancer Drugs / LDHs Nanocomposites

Layered double hydroxides (LDHs for short) consist of stacks of positively charged octahedral main sheets and the exchangeable interlayer anions, is widely used as a new drug carrier in biomedical materials area for its high safety, good bi-ocompatibility, effective targeting, exchangeability of interlayer anionic and so on. Here we chose Methotrexate (MTX) as our guest molecule, and Mg-Al-LDHs or Zn-Al-LDHs as host materials to synthesize a series of MTX/LDHs nanocompounds by different methods, and systematically investigate the effect of different synthesized conditions on the morphology and in vitro release property. Further, we chose the samples having suitable particle size for anticancer efficacy tests (MTT assay). The details are summarized as following:1. Zn-Al-MTX/LDHs nanocompounds were prepared by the coprecipitation method to form uniform morphology, and the influence of solvent, pH, R value on the properties of nanocompounds were studied systematically, then the release performance was studied, finally, the particles possessing appropriate particle size were select to be determined by MTT test. The results showed that product with better morphology, slow-release performance and suitable particle size which met the biological cell activity experiment could be synthesized by controlling the appropriate R value in the mixture of ethanol/water system with pH=8.5. The anticancer efficacy tests for the MTX/LDHs compounds turn out to be more effective in cell suppression compared to the MTX itself, and the smaller the particle size is, the better anticancer efficacy could be within a certain range.2. Mg-Al-MTX/LDHs intercalation compounds with sphere-like morphology were synthesized in quaternary water/oil (W/O) reverse microemulsion solution containing the mixture of Span-80and Tween-80, cyclohexane, n-butyl alcohol and aqueous solution. Furthermore, the drug-release properties and release mechanism of prepared samples were studied. It indicates that the average particle size increases with the increase of ω value, and the fitting coefficients of parabolic diffusion model are the highest, showing that MTX/LDHs in vitro release belongs to multi phase diffusion process via ion exchange. The evaluation of anticancer efficiency of MTX/LDHs nanocompounds indicated that products with smaller particle size show better tumor suppression effect, due to the fact that the smaller particles could permeate the cell membrane much easier.3. Zn-Al-MTX/LDHs nanocompounds were prpared by mechanical method, ion exchange method, and reverse microemulsion method respectively, and the experiment orthogonal design was used to compare the properties of MTX/LDHs prepared from different methods. The result illustrated the particles show thin sheet formation from mechanical method, and irregular filiform structure when certain amount of surfactants added. While big particles (about1μm) were obtained by ion exchange method, and the particles with much more regular morphology could be synthesized in a water-in-oil reverse microemulsion by controlling R values.