Kuo Yung-Chih, Lin Ching-Chun
Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China.
Int J Nanomedicine. 2015 Apr 1;10:2653-72. doi: 10.2147/IJN.S79528. eCollection 2015.
Liposomes with cardiolipin (CL) and wheat germ agglutinin (WGA) were developed to permeate the blood-brain barrier and treat Alzheimer's disease. WGA-conjugated and CL-incorporated liposomes (WGA-CL-liposomes) were used to transport nerve growth factor (NGF) and curcumin (CUR) across a monolayer of human brain-microvascular endothelial cells regulated by human astrocytes and to protect SK-N-MC cells against apoptosis induced by β-amyloid1-42 (Aβ(1-42)) fibrils. An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aβ(1-42), but decreased the atomic ratio of nitrogen to phosphorus and release of CUR. In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood-brain barrier, but reduced the absolute zeta potential value and biocompatibility. WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood-brain barrier and inhibiting neurotoxicity.
开发了含有心磷脂(CL)和麦胚凝集素(WGA)的脂质体,以穿透血脑屏障并治疗阿尔茨海默病。将WGA偶联并掺入CL的脂质体(WGA-CL-脂质体)用于在由人星形胶质细胞调节的人脑微血管内皮细胞单层中转运神经生长因子(NGF)和姜黄素(CUR),并保护SK-N-MC细胞免受β-淀粉样蛋白1-42(Aβ(1-42))原纤维诱导的细胞凋亡。脂质中CL摩尔百分比的增加会增加脂质体直径、绝对zeta电位值、NGF和CUR的包封率、NGF的释放、生物相容性以及SK-N-MC细胞与Aβ(1-42)的活力,但会降低氮磷原子比和CUR的释放。此外,用于接枝的WGA浓度的增加会增加脂质体直径、氮磷原子比以及NGF和CUR穿过血脑屏障的通透性,但会降低绝对zeta电位值和生物相容性。携带NGF和CUR的WGA-CL-脂质体有望成为未来临床应用中靶向血脑屏障和抑制神经毒性的胶体递送载体。