title: Facile synthesis of methotrexate intercalated layered double hydroxides: particle control, structure and bioassay explore.
abstract: To study the influence of particle size on drug efficacy and other properties, a series of methotrexate intercalated layered double hydroxides (MTX/LDHs) were synthesized through the traditional coprecipitation method, using a mixture of water and polyethylene glycol (PEG-400) as the solvent. To adjust the particle size of MTX/LDHs, the dropping way, the volume ratio of water to PEG-400 and different hydrothermal treatment time changed accordingly, and the results indicate that the particle size can be controlled between 90 and 140 nm. Elemental C/H/N and inductive coupled plasma (ICP) analysis indicated that different synthesis conditions almost have no effect on the compositions of the nanohybrids. X-ray diffraction (XRD) patterns manifested the successful intercalation of MTX anions into the LDH interlayers, and it's also found out that different volume ratios of water to PEG-400 and variable dropping way can affect the crystallinity of the final samples, i.e., the volume ratio of 3:1 and pH decreasing are proved to be optimum conditions. Furthermore, both antiparallel monolayer and bilayers adopting different orientations are suggested for four samples from XRD results. Fourier transform infrared spectroscopy (FTIR) investigations proved the coexistence of CO3(2-) and MTX anions in the interlayer of the nanohybrids. MTX/LDH particles exhibited hexagonal platelet morphology with round corner and different dropping ways can affect the morphology greatly. Moreover, a DSC study indicated that longer time treatment can weaken the bond between the MTX anions and LDH layers. The kinetic release profiles told us that larger MTX/LDH particles have enhanced the ability of LDH layers to protect interlayer molecules. At last, the bioassay study indicated that the nanohybrids with larger diameters have higher tumor suppression efficiency.
authors.affiliation: Jiangsu Key Laboratory of Biofunctional Material, College of Chemistry and Material Science, Nanjing Normal University, Nanjing 210023, PR China.
authors.forename: De-Ying
authors.initials: DY
authors.lastname: Tian
authors.affiliation: Jiangsu Key Laboratory of Biofunctional Material, College of Chemistry and Material Science, Nanjing Normal University, Nanjing 210023, PR China.
authors.forename: Zhen-Lei
authors.initials: ZL
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Biofunctional Material, College of Chemistry and Material Science, Nanjing Normal University, Nanjing 210023, PR China. Electronic address: lishuping@njnu.edu.cn.
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Biofunctional Material, College of Chemistry and Material Science, Nanjing Normal University, Nanjing 210023, PR China; Shenzhen Research Institute of Xiamen University, Shenzhen 518057, PR China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D065546:Drug Liberation; D006801:Humans; D006878:Hydroxides / Q000138:chemical synthesis / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry*; D008727:Methotrexate / Q000737:chemistry* / Q000633:toxicity; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D006878:Hydroxides; D007364:Intercalating Agents; D014867:Water; D011092:Polyethylene Glycols; D008727:Methotrexate
keywords: Bioassay test; Layered double hydroxides; Methotrexate; Nanohybrids; Release properties