甲氨蝶呤/层状双金属氢氧化物的性能调控及细胞生物实验研究

Controllable Synthesis of Methotrexatum/Layered Double Hydroxide Nanohybrids to Improve Their Anticancer Efficacy

在乙醇-水混合体系中,以氨水为沉淀剂共沉淀合成了甲氨蝶呤/层状双金属氢氧化物(MTX/LDH)纳米复合物,采用控制水热处理时间的方式来调控其性能。利用X-射线衍射(XRD)、透射电镜(TEM)和红外光谱(FT-IR)等表征手段,对其结构及形貌进行了表征。研究表明:MTX分子以单层倾斜或垂直方式插入LDH层间,随着水热处理时间的不同,MTX在层间的倾斜角度发生了变化;水热处理时间对产物的结晶度、粒径和层间排列方式都有影响,当水热处理时间为12h时,得到的MTX/LDH纳米复合物的结晶度最高,单分散性最好。在磷酸缓冲液中考察了MTX/LDH纳米复合物的缓释性能,结果表明样品均呈现出良好的缓释性能,释放速率先快后慢。重点考察了这几种MTX/LDH纳米复合物作用于肺癌细胞A549的细胞生物实验,研究表明这几种复合物对肺癌细胞A549都具有良好的抑制作用,其效果与纳米复合物的单分散性和粒径有密切的关系,单分散性越好,粒径分布越均匀,对A549癌细胞的抑制效果越好。

The Methotrexatum/Layered Double Hydroxide （MTX/LDH） nanohybrids with different properties were prepared by controlling the hydrothermal duration,using the coprecipitation method in alcohol-water solvent and NH3·H2O as precipitator.The structure and morphologies of MTX/LDH were systematically characterized by X-ray diffraction （XRD）,transmission electron micrograph （TEM） and fourier transform infrared spectroscopy （FT-IR）.Results showed that MTX molecules were intercalated into LDH interlayers as a declining or perpendicular monolayer with the variation of hydrothermal treatment.Indeed,the crystallinity degree （indicated by the sharpness of the diffraction peaks） and particle size were also affected by the hydrothermal duration.The results indicated that MTX/LDH nanohybrids can be synthesized with the highest quality （morphology,monodispersity and crystallinity） at 100 ℃ for 12 h.The high drug-loading capacity of all the nanohybrids indicated that pristine LDH is a good carrier and it seems that capacity has no relation with the particle size.In addition,in vitro release tests of the drugs intercalated into LDH were explored in phosphate buffered saline （PBS） with pH=7.4,and four dissolution-diffusion kinetic models were used to fit the release process.The results indicated that the nanohybrids present two-step release process,i.e.,initially fast and then the controlled-release,probably suitable for clinic application.Furthermore,the modified parabolic diffusion model can simulate the release progress better,indicating that MTX/LDH in vitro release process belongs to multi-phase diffusion process via ion exchange.At last,the anticancer efficacy of MTX/LDH hybrids was estimated by the bioassay such as MTT with the human lung cancer （A549）.Accooring to the cell-line tests,the drug efficacy is associated with dispersion coefficient ε closely：the smaller ε is,the better the tumor suppression efficiency becomes.The parameter ε is determined by both the monodispersity and the particle size.