Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Sichuan, People's Republic of China.
J Drug Target. 2010 Aug;18(7):557-66. doi: 10.3109/10611861003599461.
For the purpose of clinical intravenous injection of 10-hydroxycamptothecin, a novel formulation of lipid nanoparticles loaded with 10-hydroxycamptothecin-phospholipid complex (HCPT-PC-LNs) was prepared by solvent evaporation and high-pressure homogenization methods. Spherical particles with a mean particle size of 200 nm and high encapsulation efficiency of 97.39 +/- 0.91% could be achieved under optimal conditions. In vitro release profile showed that the release pattern of HCPT from nanoparticles was retarded with neglectable initial burst release and well-fitted to Ritger-Peppas equation. In vivo distribution studies in mice showed that HCPT-PC-LNs were mainly localized in liver. Besides, in situ mouse hepatoma model was established and tumor uptake of HCPT-PC-LNs was much higher than that of free HCPT (more than 18-fold). It was found that HCPT-PC-LNs exhibited high growth inhibitory effect on human liver cancer cells by MTT assay. The cellular uptake of HCPT was 24.33 +/- 1.30 x 10(-7) microg/cell in HCPT-PC-LNs treated group at 12 h, which was almost 14-fold higher than that of free HCPT (1.72 +/- 0.57 x 10(-7) microg/cell). This study suggested that the HCPT-PC-LNs could be utilized as a novel formulation for liver tumors therapy, which might be applied in clinic in the near future.
为了实现 10-羟基喜树碱的临床静脉注射，采用溶剂蒸发和高压匀质法制备了载有 10-羟基喜树碱-磷脂复合物（HCPT-PC-LN）的脂质纳米粒的新型制剂。在最佳条件下，可以得到平均粒径为 200nm 的球形颗粒，且包封效率高达 97.39%±0.91%。体外释放结果表明，纳米粒中 HCPT 的释放模式具有明显的缓释效果，初始突释可以忽略不计，且符合 Ritger-Peppas 方程。在小鼠体内分布研究中，HCPT-PC-LN 主要定位于肝脏。此外，还建立了原位小鼠肝癌模型，结果表明 HCPT-PC-LN 的肿瘤摄取量明显高于游离 HCPT（超过 18 倍）。MTT 实验结果表明，HCPT-PC-LN 对人肝癌细胞具有较强的生长抑制作用。在 12 h 时，HCPT-PC-LN 处理组细胞摄取 HCPT 的量为 24.33±1.30×10(-7)μg/cell，几乎是游离 HCPT（1.72±0.57×10(-7)μg/cell）的 14 倍。本研究表明，HCPT-PC-LN 可作为一种新型肝肿瘤治疗制剂，有望在不久的将来应用于临床。
