Laboratoire de Pharmacie Galénique, Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris Cedex, France.
J Liposome Res. 2009;19(4):287-300. doi: 10.3109/08982100902838682.
An original ligand (Lac-10-Chol) designed to interact with asialoglycoprotein receptors to potentially target hepatocyte was synthesised by grafting a lactose head to a cholesteryl structure, which was then included in liposomes. Preliminary formulation tests led to the selection of conventional formulations based on soybean phosphatidylcholine/cholesterol/DOTAP (+/- DOPE) (+/- Lac-10-Chol) that present reproducible absolute entrapment value (1.45 +/- 0.10%), with a size of 109 +/- 7 nm and a slight positive charge (3.77 +/- 1.59 mV). Cell viability (via the MTT test), expressed as the percentage of nontreated cells in HepG2 cells, was very close to the control. Internalization tests evidenced an intracellular penetration of fluorescent liposomes, but no specific ligand effect was demonstrated (P > 0.05). Nevertheless, regarding the adenosine triphosphate (ATP) assay, a slight increase was obtained with liposome loaded with ATP incorporating Lac-10-chol after 24 hours (P < 0.05).
设计了一种原始配体（Lac-10-Chol），通过将乳糖头接到胆固醇结构上来与去唾液酸糖蛋白受体相互作用，从而潜在地靶向肝细胞，然后将其包含在脂质体中。初步配方测试导致选择了基于大豆卵磷脂/胆固醇/DOTAP（+/- DOPE）（+/- Lac-10-Chol）的常规配方，这些配方具有可重复的绝对包封值（1.45 +/- 0.10%），大小为 109 +/- 7nm，带轻微正电荷（3.77 +/- 1.59 mV）。通过 HepG2 细胞中的未处理细胞百分比表示的细胞活力（通过 MTT 试验）非常接近对照。内化试验证明了荧光脂质体的细胞内穿透，但未证明特定配体的作用（P > 0.05）。尽管如此，关于三磷酸腺苷（ATP）测定，在用含有 Lac-10-chol 的 ATP 加载的脂质体孵育 24 小时后，获得了轻微的增加（P < 0.05）。
