Different Morphologies Of Anticancer Drugs / LDHs Nanocomposites Release Properties

Layered double hydroxides (LDHs) are the only known inorganic materials with positive layer charge, their structural units are made from stacks of positively charged octahedral sheets and the exchangeable interlayer anions. It can realize controlled release of drugs by electrostatic interaction, hydrogen bond effect and space steric effect between layers and interlayer anions. In recent years, LDHs have been focused as a new type of nanomaterial drug carrier in biomedical materials area, but there are still many problems need to be solved, now. We choose Methotrexate (MTX) as our guest molecule, and Mg-Al-LDHs as layered carrier, to synthesize a series of MTX/LDHs nanocompounds and examine its properties. In this paper, we focus our study on the influence of particle size and morphology on drug-loading capacity and control-release properties of MTX/LDHs nanocompounds. The exploratory research has been carried on the formation mechanism of LDHs synsthsised by mechanochemical approach, too. The details are summarized as following:1. MTX was intercalated into the LDHs by the coprecipitation method to form uniform morphology of MTX/LDHs nanocompounds, the effect of different solvents and dropping methods the properties of MTX/LDHs nanocompounds has been examined carefully. Compared with the product prepared in other solvents, the particles obtained in the mixture of PEG-400and water exhibited round plates with the best monodispersity and the most regular morphology. Due to the inhibition effect of PEG-400, further agglomeration will be forbidden; as a result the monodispersity will be improved. Research results show that by using the pH dropping method and the volume ratio of1:3of PEG-400/water as the solvent, the MTX/LDHs nanocompounds with high crystallinity will be formed. The in vitro release result revealed that the release property of MTX/LDHs can be well described by parabolic diffusion equation, or rather, the release mechanism is mainly belongs to drug diffusion.2. By controlling the synthesis conditions of the experimental, the relationship between particle size and hydrothermal treatment conditions (i.e., time and temperature) has been systematically investigated, and the results indicate that the particle size can be precisely controlled. The crystallinity of MTX/LDHs will be affected by particle size, and the in vitro release shows that bigger particles have much longer release duration and the release data can be well described by Rigter-Peppas equation or parabolic diffusion model.3. Hexagonal platelet morphology of MTX/LDHs compounds was synthesized by ion exchange method. The optimum experimental conditions to obtain high crystallinity and drug-loading capacity nanocompounds by orthogonal experiment are as follows:mLDHs:mMTx=2:1, pH=9.5, ion exchange under80℃for3days. The products synthesized by solvothermal method present petal shape or watercaltrop morphology. The release properties shows that round plates product has better slow-release property than hexagonal platelet morphology, and the petal shape or watercaltrop morphology products are a little poorer than others.4. A mechanochemical approach is used to prepare LDHs. The study indicates that grinding leads to the incomplete formation of LDHs phase, LDHs-M. The reaction degree of precursor salts to LDHs after grinding depends on the melting points of the precursors. As expected, hydrothermal treatment is beneficial for the good crystallization and regularity of LDHs. Especially, the effect of hydrothermal treatment has been emphatically explored. The hydration of LDHs-M, increment of zeta potentials and the complete exchange of NO3-by CO32-anions occur successively or in parallel during the hydrothermal treatment. It can be found that combination of grinding and hydrothermal treatment gives rise to the formation of uniform and monodispersed particles of LDHs.