Wu Minming, Guo Kai, Dong Hongwei, Zeng Rong, Tu Mei, Zhao Jianhao
Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, PR China.
Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, PR China.
Mater Sci Eng C Mater Biol Appl. 2014 Dec;45:162-9. doi: 10.1016/j.msec.2014.09.008. Epub 2014 Sep 16.
Novel biomimetic amphiphilic chitosan derivative, deoxycholic acid-phosphorylcholine-chitosan conjugate (DCA-PCCs) was synthesized based on the combination of Atherton-Todd reaction for coupling phosphorylcholine (PC) and carbodiimide coupling reaction for linking deoxycholic acid (DCA) to chitosan. The chemical structure of DCA-PCCs was characterized by (1)H and (31)P nuclear magnetic resonance (NMR). The self-assembly of DCA-PCCs in water was analyzed by fluorescence measurements, dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM) technologies. The results confirmed that the amphiphilic DCA-PCCs can self-assemble to form nanosized spherical micelles with biomimetic PC shell. In vitro biological evaluation revealed that DCA-PCCs micelles had low toxicity against NIH/3T3 mouse embryonic fibroblasts as well as good hemocompatibility. Using quercetin as a hydrophobic model drug, drug loading and release study suggested that biomimetic DCA-PCCs micelles could be used as a promising nanocarrier avoiding unfavorable biological response for hydrophobic drug delivery applications.
基于用于偶联磷酰胆碱（PC）的Atherton-Todd反应和用于将脱氧胆酸（DCA）连接到壳聚糖的碳二亚胺偶联反应，合成了新型仿生两亲性壳聚糖衍生物——脱氧胆酸-磷酰胆碱-壳聚糖共轭物（DCA-PCCs）。通过氢核磁共振（¹H NMR）和磷核磁共振（³¹P NMR）对DCA-PCCs的化学结构进行了表征。利用荧光测量、动态激光光散射（DLS）、zeta电位和透射电子显微镜（TEM）技术分析了DCA-PCCs在水中的自组装情况。结果证实，两亲性DCA-PCCs能够自组装形成具有仿生PC外壳的纳米级球形胶束。体外生物学评价表明，DCA-PCCs胶束对NIH/3T3小鼠胚胎成纤维细胞具有低毒性以及良好 的血液相容性。以槲皮素作为疏水模型药物进行的载药和释药研究表明，仿生DCA-PCCs胶束可作为一种有前景的纳米载体，用于疏水药物递送应用，避免不良生物学反应。
