不同溶剂对甲氨蝶呤/类水滑石复合物性质的影响
收稿日期: 2012-11-15
网络出版日期: 2012-12-06
基金资助
项目受国家自然科学基金(No. 21073093);高等学校博士点专项科研基金(No. 20103207120006)和江苏高校优势学科建设工程项目资助.
Influence of Different Solvents on the Property of Methotrexate/Layered Double Hydroxides
Received date: 2012-11-15
Online published: 2012-12-06
Supported by
Project supported by the National Natural Science Foundation of China (No. 21073093), Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20103207120006) and the Priority Academic Program Development of the Jiangsu Higher Education Institutions of China.
采用共沉淀法将甲氨蝶呤(MTX)插层组装到类水滑石(LDHs)层间, 分别考察了不同溶剂(如: 水、乙醇/水、聚乙二醇-400/水、聚乙二醇-4000/水)对合成的甲氨蝶呤/类水滑石(MTX/LDHs)纳米复合物性质的影响. 利用透射电镜(TEM)和原子力显微镜(AFM)观察产物形貌, 利用X-射线衍射(XRD)、傅里叶变换红外(FTIR)、热重/差式扫描量热(TG-DSC)和紫外光谱(UV-Vis)等表征手段, 对纳米复合物的结构及热力学性质进行了系统的研究. 在pH=7.4的磷酸盐缓冲溶液中测定不同时间点药物累积释放量, 考察了不同溶剂中合成的MTX/LDHs纳米复合物的药物控释性能. 结果表明, 短链聚乙二醇的加入保证了纳米粒子的稳定生长, 能有效控制产物形貌, 合成出的产物呈规则的圆片状, 单分散性好, 药物缓释性能平稳, 释放过程属于药物扩散控制过程. 当聚乙二醇分子链过长时, 由于其自身容易发生缠绕, 反而不利于纳米粒子的生长.
张晓晴 , 曾美桂 , 李淑萍 . 不同溶剂对甲氨蝶呤/类水滑石复合物性质的影响[J]. 化学学报, 2013 , 71(02) : 246 -254 . DOI: 10.6023/A12110921
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 examined carefully. The nanocompounds were then characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (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 characterization. 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 molecules 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 nanocompounds 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.
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