Institute of Biology, Leiden University, 2333 CC Leiden, The Netherlands.
Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands.
Cells. 2022 Feb 15;11(4):671. doi: 10.3390/cells11040671.
Glucocorticoids (GCs) are effective anti-inflammatory drugs, but their clinical use is limited by their side effects. Using liposomes to target GCs to inflammatory sites is a promising approach to improve their therapeutic ratio. We used zebrafish embryos to visualize the biodistribution of liposomes and to determine the anti-inflammatory and adverse effects of the GC prednisolone phosphate (PLP) encapsulated in these liposomes. Our results showed that PEGylated liposomes remained in circulation for long periods of time, whereas a novel type of liposomes (which we named AmbiMACs) selectively targeted macrophages. Upon laser wounding of the tail, both types of liposomes were shown to accumulate near the wounding site. Encapsulation of PLP in the PEGylated liposomes and AmbiMACs increased its potency to inhibit the inflammatory response. However, encapsulation of PLP in either type of liposome reduced its inhibitory effect on tissue regeneration, and encapsulation in PEGylated liposomes attenuated the activation of glucocorticoid-responsive gene expression throughout the body. Thus, by exploiting the unique possibilities of the zebrafish animal model to study the biodistribution as well as the anti-inflammatory and adverse effects of liposomal formulations of PLP, we showed that PEGylated liposomes and AmbiMACs increase the therapeutic ratio of this GC drug.
糖皮质激素（GCs）是有效的抗炎药物，但由于其副作用，其临床应用受到限制。利用脂质体将 GCs 靶向炎症部位是提高治疗效果的一种有前途的方法。我们使用斑马鱼胚胎来可视化脂质体的生物分布，并确定包封在这些脂质体中的 GC 泼尼松龙磷酸盐（PLP）的抗炎和不良反应。我们的结果表明，聚乙二醇化脂质体在循环中长时间保留，而一种新型脂质体（我们称为 AmbiMACs）则选择性地靶向巨噬细胞。在尾巴激光损伤后，这两种脂质体都被证明在损伤部位附近聚集。将 PLP 包封在聚乙二醇化脂质体和 AmbiMACs 中增加了其抑制炎症反应的效力。然而，将 PLP 包封在任何一种脂质体中都会降低其对组织再生的抑制作用，而将 PLP 包封在聚乙二醇化脂质体中则会减弱全身糖皮质激素反应基因表达的激活。因此，通过利用斑马鱼动物模型研究 PLP 的脂质体制剂的生物分布以及抗炎和不良反应的独特可能性，我们表明聚乙二醇化脂质体和 AmbiMACs 提高了这种 GC 药物的治疗效果。
