Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
Drug Deliv. 2010 Apr;17(3):114-22. doi: 10.3109/10717540903580176.
This study intended to prepare liver-targeting solid lipid nanoparticles (SLNs) with a hepatoprotective drug, cucurbitacin B (Cuc B), using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA). The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The Cuc B-loaded galactosylated and conventional SLNs were successfully prepared by a high-pressure homogenization method. The two SLNs showed similar physical and pharmaceutical properties, including: the particle size measured by laser diffraction was 135 nm for galactosylated SLN (GalSLN) and 123 nm for conventional SLNs (CSLN); zeta potentials were -31.6 mV (GalSLN) and -34.3 mV(CSLN); in vitro release behavior of the two SLNs was similar, and both showed the biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards. In contrast, the two SLNs demonstrated a marked difference in in vitro cellular cytotoxicity and in vivo tissue distribution performances. The IC(50) values of Cuc B in the two SLNs were by far lower than those of Cuc B solution and further Cuc B-GalSLN had about half the IC(50) value of Cuc B-CSLN. These results indicated that the encapsulation of Cuc B in SLNs resulted in the enhancement of cytotoxic activity, and galactosyl ligand could further enhance the cellular accumulation and cytotoxicity of Cuc B. The weighted-average overall drug targeting efficiency (Te) was used to evaluate the liver targetability. Cuc B-GalSLN gave a relatively high (Te)(liver) value of 63.6%, approximately 2.5-times greater than that of Cuc B-CSLN (25.3%) and Cuc B solution (23.8%). In summary, the incorporation of N-HLBA into SLNs significantly enhanced the liver targetability of Cuc B-loaded SLNs and GalSLN had a great potential as a drug delivery carrier for improved liver targetability.
本研究旨在制备具有肝靶向性的固体脂质纳米粒（SLN），载药为葫芦素 B（Cuc B），使用半乳糖化脂质 N-十六烷基乳糖酰胺（N-HLBA）。半乳糖化脂质 N-HLBA 通过乳糖酸的内酯形式中间体制备，并通过将半乳糖连接到十六烷基胺脂质来合成。通过高压匀浆法成功制备了载药的半乳糖化和常规 SLN。两种 SLN 表现出相似的物理和药学性质，包括：通过激光衍射测量的粒径分别为 135nm 的半乳糖化 SLN（GalSLN）和 123nm 的常规 SLN（CSLN）；Zeta 电位分别为-31.6mV（GalSLN）和-34.3mV（CSLN）；两种 SLN 的体外释放行为相似，均表现出双相药物释放模式，初始阶段突释，随后持续释放。相比之下，两种 SLN 在体外细胞毒性和体内组织分布性能方面表现出明显差异。两种 SLN 中 Cuc B 的 IC50 值远低于 Cuc B 溶液，进一步表明 Cuc B-GalSLN 的 IC50 值约为 Cuc B-CSLN 的一半。这些结果表明，将 Cuc B 包封在 SLN 中导致细胞毒性活性增强，半乳糖配体可进一步增强 Cuc B 的细胞积累和细胞毒性。加权平均总药物靶向效率（Te）用于评估肝靶向性。Cuc B-GalSLN 的相对较高的（Te）（肝）值为 63.6%，约为 Cuc B-CSLN（25.3%）和 Cuc B 溶液（23.8%）的 2.5 倍。总之，N-HLBA 掺入 SLN 显著增强了载药 SLN 的肝靶向性，GalSLN 作为提高肝靶向性的药物载体具有很大的潜力。
