基于UGI反应制备海藻酸衍生物及其载药微胶囊的释药性  

Preparation of alginate derivatives via UGI reaction and their drug-loaded microcapsules for drug delivery

作　　者：陈秀琼 冯美西 李正月 颜慧琼[1,2,3] 林强 CHEN Xiuqiong;FENG Meixi;LI Zhengyue;YAN Huiqiong;LIN Qiang(Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education,Hainan Normal University,Haikou 571158,Hainan,China;Key Laboratory of Natural Polymer Functional Materials of Haikou,Haikou 571158,Hainan,China;Key Laboratory of Water Pollution Treatment and Resource Reuse of Hainan Province,Haikou 571158,Hainan,China)

机构地区：[1]海南师范大学热带药用植物化学教育部重点实验室,海南海口571158 [2]海口市天然高分子功能材料重点实验室,海南海口571158 [3]海南省水环境污染治理与资源化重点实验室,海南海口571158

出　　处：《精细化工》2021年第3期585-592,共8页Fine Chemicals

基　　金：国家自然科学基金项目(51963009);海南省自然科学基金项目(219QN209);海南省高等学校科学研究项目(Hnky2019-36);海南省重点研发项目(ZDYF2019018)。

摘　　要：将海藻酸钠(SA)、正辛胺、对甲苯磺酰甲基异腈和甲醛(或正丙醛)通过UGI 4组分缩合反应制备海藻酸衍生物Ugi-Alg-1和Ugi-Alg-2。通过FTIR和1HNMR对Ugi-Alg的结构进行表征,并采用TGA、XRD、荧光光谱(FM)、表面张力(SFT)、TEM、激光粒度和Zeta电位分析仪对其性能进行测试。结果表明,通过UGI反应成功制备了Ugi-Alg-1和Ugi-Alg-2。疏水侧基的接枝破坏了SA的分子内氢键,使其微晶结构发生改变,热稳定性下降,分子链的灵活性增强。Ugi-Alg-1和Ugi-Alg-2的分子链可通过疏水缔合作用发生自由卷曲,形成水动力学粒径(dH)分别为659.4和534.6 nm、Zeta电位分别为–54.6和–60.8 mV的胶束状聚集体,说明Ugi-Alg-1和Ugi-Alg-2均具有较好的胶体界面活性。并且Ugi-Alg-1和Ugi-Alg-2的疏水内腔能有效地增溶疏水性的布洛芬,迟滞药物的扩散,使药物释放速率减慢。Ugi-Alg载药微胶囊对布洛芬的释药过程符合Non-Fickian扩散机制,说明Ugi-Alg微胶囊溶胀降解与其负载的药物扩散共同控制布洛芬药物的释放速率。同时,Ugi-Alg载药微胶囊能够表现出良好的细胞相容性。Alginate derivatives,Ugi-Alg-1 and Ugi-Alg-2 were synthesized by UGI four-component condensation reaction from sodium alginate(SA),n-octylamine,p-tolylsulfonylmethyl isocyanide and formaldehyde(or n-propionaldehyde).The structures were characterized by FTIR and 1HNMR,and the properties were tested by TGA,XRD,fluorescence spectrum(FM),surface tension(SFT),TEM,laser particle size and Zeta potential analyzers.The results showed that Ugi-Alg-1 and Ugi-Alg-2 were successfully prepared by UGI reaction.The grafting of hydrophobic side groups broke the intra-molecular hydrogen bonds of SA,resulting in the change of its microcrystalline structure,the decrease of thermal stability,and the improvement of the flexibility of its molecular chain.Moreover,the molecular chains of Ugi-Alg-1 and Ugi-Alg-2 could curl freely through hydrophobic association to form the micellar aggregates with hydrodynamic particle diameter(dH)of 659.4 and 534.6 nm,and Zeta potential of–54.6 and–60.8 mV,respectively.These results indicated that both Ugi-Alg-1 and Ugi-Alg-2 had good colloidal interfacial activity.In addition,the hydrophobic cavities of Ugi-Alg-1 and Ugi-Alg-2 could effectively solubilize hydrophobic ibuprofen,retard the diffusion of drugs,and slow down the drug release rate.The release process of ibuprofen from Ugi-Alg drug-loaded microcapsules conformed to the Non-Fickian diffusion mechanism,indicating that the swelling and degradation of Ugi-Alg microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen.Furthermore,Ugi-Alg drug-loaded microcapsules displayed good cell compatibility.

关 键 词：UGI反应 海藻酸衍生物 对甲苯磺酰甲基异腈 载药微胶囊 缓释性能 医药原料 

分 类 号：O636.1[理学—高分子化学] TQ460.4[理学—化学]