Xiao Gao-Fei, Zeng Hong-Yan, Huang Qing-Jun, Zhang Wei, Du Jin Ze, Duan Heng Zhi, Chen Chao Rong
College of Chemical Engineering, Xiangtan University, Xiangtan, Hunan, 411105, China.
J Nanosci Nanotechnol. 2018 Aug 1;18(8):5256-5265. doi: 10.1166/jnn.2018.15408.
Mg-Al-NO3 hydrotalcite (p-LDH) was employed as a carrier for the controlled release of 5-Fluorouracil (5-FU). The p-LDH was pretreated by acid-pretreatment to gain a more stable material (a-LDH) in acid medium for oral administration. It demonstrated that the a-LDH had smaller crystal size, particle sizes and higher permanent charge density (σp) compared with that of the p-LDH by means of XRD, SEM, FT-IR, UV-vis DRS, TG-DSC, BET/BJH and other techniques. The FU/a-LDH and FU/p-LDH delivery systems were obtained using anion-exchange method. The in vitro 5-FU drug release studies showed that no burst release phenomenon was observed at the beginning of release tests. The in vitro 5-FU release behaviors of the delivery systems at initial pH 4.6 and 7.5 were studied which could be described by first-order and Bhaskas models. Combined with the XRD and FT-IR analyses of the solid residues of the FU/a-LDH and FU/p-LDH after the release, it was found that the dissolution mechanism was mainly responsible for the release behavior of the FU/p-LDH at initial 4.6, while the anion-exchange between intercalated 5-FU and phosphate anions mechanism was responsible for the FU/a-LDH at pH 4.6 and 7.5 as well as FU/p-LDH at pH 7.5. It is concluded that the hydrotalcites could be used as the basis of a tunable drug delivery carrier for 5-FU.
镁铝硝酸根水滑石(p-LDH)被用作5-氟尿嘧啶(5-FU)控释的载体。通过酸预处理对p-LDH进行预处理,以获得在酸性介质中更稳定的材料(a-LDH)用于口服给药。通过XRD、SEM、FT-IR、UV-vis DRS、TG-DSC、BET/BJH等技术表明,与p-LDH相比,a-LDH具有更小的晶体尺寸、粒径和更高的永久电荷密度(σp)。采用阴离子交换法获得了FU/a-LDH和FU/p-LDH递送系统。体外5-FU药物释放研究表明,在释放试验开始时未观察到突释现象。研究了递送系统在初始pH 4.6和7.5时的体外5-FU释放行为,其可以用一级模型和Bhaskas模型来描述。结合释放后FU/a-LDH和FU/p-LDH固体残渣的XRD和FT-IR分析,发现溶解机制是FU/p-LDH在初始pH 4.6时释放行为的主要原因,而插层的5-FU与磷酸根阴离子之间的阴离子交换机制是pH 4.6和7.5时FU/a-LDH以及pH 7.5时FU/p-LDH释放行为的主要原因。结论是水滑石可作为5-FU可调谐药物递送载体的基础。