Department of Pharmaceutics, Shenyang Pharmaceutical University, Liaoning, China.
Biomaterials. 2010 Feb;31(5):908-15. doi: 10.1016/j.biomaterials.2009.09.104. Epub 2009 Oct 22.
Trimethylated chitosan (TMC) surface-modified poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (TMC/PLGA-NP) were synthesized as a drug carrier for brain delivery. TMC was covalently coupled to the surface of PLGA nanoparticles (PLGA-NP) via a carbodiimide-mediated link. The zeta potential of TMC/PLGA-NP was about 20mV with a mean diameter around 150nm. 6-coumarin loaded PLGA-NP and TMC/PLGA-NP were injected into the caudal vein of mice, and fluorescent microscopy of brain sections showed a higher accumulation of TMC/PLGA-NP in the cortex, paracoele, the third ventricle and choroid plexus epithelium, while no brain uptake of PLGA-NP was observed. There was no pronounced difference in cell viability between TMC/PLGA-NP and PLGA-NP as shown by MTT assay. Behavioral testing showed that the injection of coenzyme Q(10) loaded TMC/PLGA-NP greatly improved memory impairment, restoring it to a normal level, but the efficacy was slight for loaded PLGA-NP, without TMC conjugation. The senile plaque and biochemical parameter tests confirmed the brain-targeted effects of TMC/PLGA-NP. These experiments show that TMC surface-modified nanoparticles are able to cross the blood-brain barrier and appear to be a promising brain drug delivery carrier with low toxicity.
三甲基壳聚糖（TMC）表面修饰的聚（D，L-乳酸-共-乙醇酸）（PLGA）纳米粒子（TMC/PLGA-NP）被合成作为一种用于脑内递送的药物载体。TMC 通过碳二亚胺介导的键合共价偶联到 PLGA 纳米粒子（PLGA-NP）的表面。TMC/PLGA-NP 的 ζ 电位约为 20mV，平均直径约为 150nm。6-香豆素负载的 PLGA-NP 和 TMC/PLGA-NP 被注入小鼠尾静脉，脑切片的荧光显微镜显示 TMC/PLGA-NP 在皮质、旁脑室、第三脑室和脉络丛上皮中的积累更高，而没有观察到 PLGA-NP 的脑摄取。MTT 测定显示 TMC/PLGA-NP 和 PLGA-NP 之间的细胞活力没有明显差异。行为测试表明，辅酶 Q(10)负载的 TMC/PLGA-NP 的注射极大地改善了记忆障碍，使其恢复到正常水平，但负载 PLGA-NP 的效果轻微，没有 TMC 缀合。老年斑和生化参数测试证实了 TMC/PLGA-NP 的脑靶向作用。这些实验表明，TMC 表面修饰的纳米粒子能够穿过血脑屏障，并且似乎是一种具有低毒性的有前途的脑内药物递送载体。
