Abstract
Methotrexate (MTX) was intercalated into the layered double hydroxides (LDHs) by the coprecipitation method to form MTX/LDHs nanocompounds, the effect of different solvents, i.e. water, mixture of ethanol and water, mixture of polyethylene glycol-400/4000 (PEG-400/4000) and water, on the properties of MTX/LDHs nanocompounds has been exam- ined carefully. The nanocompounds were then characterized by X-ray diffraction (XRD), Fourier transform infrared spec- troscopy (FTIR), transmission electron/micrograph (TEM), atomic force microscopy (AFM), thermogravimetry/differential scanning calorimetry (TG-DSC) and UV-visible diffuse spectroscopy (UV-vis). XRD and FTIR investigations demonstrated the successful intercalation of MTX anions as a declining monolayer into the interlayer of LDHs and the interlayer spacing changed accordingly with the variation in the kind of solvents. We thought that the addition of ethanol and PEG just changed the growth environment, especially the property of interlayer water in MTX/LDHs compounds and the hypothesis has been proved by the analysis of TG-DSC. There is no intercalation of PEG molecular into the LDHs interlayers from all the charac- terization. Compared with the product prepared in other solvents, the particles obtained in the mixture of PEG-400 and water exhibited round plates with the best monodispersity and the most regular morphology. The mechanism how PEG-400 mole- cules influence the formation of MTX/LDHs nanocompounds is described emphatically: non-ionized PEG-400 molecules will form chain-like structures due to the assembly in water, and the growth of nanocompounds is strictly limited in these structures. Due to the inhibition effect of PEG-400, further agglomeration will be forbidden; as a result the monodispersity will be improved. But when the molecular chain of PEG is too long (i.e. PEG-4000), it goes against the growth of nanocom- pounds on the contrary. The in vitro release experiment has been carried out in phosphate buffer solution at the pH value of 7.4, and the result revealed that the release property of MTX/LDHs can be well described by parabolic diffusion equation, or the release mechanism is mainly belongs to drug diffusion. The work reported here will help to establish a general method for the synthesis of drug/LDH nanocompounds with regular morphology and perfect dispersion properties. Keywords layered double hydroxides; polyethylene glycol; uniform particles; in vitro release
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