Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
J Control Release. 2012 May 10;159(3):429-34. doi: 10.1016/j.jconrel.2012.01.031. Epub 2012 Jan 27.
The successful treatment of central nervous system (CNS) disorders is hampered by inefficient drug delivery across the blood-brain barrier (BBB). Transferrin (Tf) could facilitate the transcytosis of coupled nanocarriers through Tf receptor (TfR) mediated pathway. In this study, Tf-modified paclitaxel-loaded polyphosphoester hybrid micells (TPM) was prepared and evaluated for its in vitro and in vivo brain-targeting efficiency. The polyphosphoester hybrid micelle formed a core-shell structure in aqueous solution, and demonstrated high drug entrapping efficiency (89.9±3.4%). In addition, the micelle showed negligible hemolysis even at 2.0 mg/mL. The TPM was 87.85±2.32 nm with ζ potentials -12.33±1.46 mV, and PTX showed sustained release from TPM. TPM demonstrated enhanced cellular uptake and brain accumulation, which were 2 and 1.8-fold of PM, respectively. TPM exhibited strongest anti-glioma activity, and the mean survival time of mice bearing intracranial U-87 MG glioma treated with TPM (39.5 days) was significantly longer than those treated with Taxol® (33.6 days). These results indicated that Tf conjugated micelle could be a promising carrier for brain-targeting drug delivery.
中枢神经系统（CNS）疾病的治疗效果不佳，其原因是药物难以有效穿透血脑屏障（BBB）。转铁蛋白（Tf）可通过转铁蛋白受体（TfR）介导途径促进偶联纳米载体的胞吞作用。在本研究中，制备了转铁蛋白修饰的紫杉醇载多磷酯混合胶束（TPM），并对其体外和体内脑靶向效率进行了评价。多磷酯混合胶束在水溶液中形成核壳结构，具有较高的载药效率（89.9±3.4%）。此外，即使在 2.0mg/mL 时，胶束的溶血率也可忽略不计。TPM 的粒径为 87.85±2.32nm，ζ电位为-12.33±1.46mV，PTX 从 TPM 中呈现持续释放。TPM 表现出增强的细胞摄取和脑内蓄积，分别是 PM 的 2 倍和 1.8 倍。TPM 表现出最强的抗神经胶质瘤活性，荷颅内 U-87MG 神经胶质瘤的小鼠经 TPM（39.5 天）治疗的平均存活时间明显长于 Taxol®（33.6 天）治疗的小鼠。这些结果表明，转铁蛋白缀合胶束可能是一种有前途的脑靶向药物传递载体。
