Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nanomedicine. 2015 Oct;11(7):1797-807. doi: 10.1016/j.nano.2015.05.007. Epub 2015 Jun 17.
Nanoparticles (NPs) are cleared by monocytes and macrophages. Chemokines CCL2 and CCL5 are key mediators for recruitment of these immune cells into tumors and tissues. The purpose of this study was to investigate effects of CCL2 and CCL5 on the pharmacokinetics (PKs) of NPs. Mice deficient in CCL2 or CCL5 demonstrated altered clearance and tissue distribution of polyethylene glycol tagged liposomal doxorubicin (PLD) compared to control mice. The PK studies using mice bearing SKOV3 ovarian cancer xenografts revealed that the presence of tumor cells and higher expression of chemokines were significantly associated with greater clearance of PLD compared to non-tumor bearing mice. Plasma exposure of encapsulated liposomal doxorubicin positively correlated with the total exposure of plasma CCL2 and CCL5 in patients with recurrent epithelial ovarian cancer treated with PLD. These data emphasize that the interplay between PLD and chemokines may have an important role in optimizing PLD therapy.
The use of nanoparticles as drug delivery carriers is gaining widespread acceptance in the clinical setting. However, the underlying pharmacokinetics of these novel drugs has not really been elucidated. In this interesting article, the authors carried out experiments using mice deficient in CCL2 or CCL5 to study the clearance of liposomal system. They showed the important role the immune system played and would enable better designs of future drug delivery systems.
纳米颗粒（NPs）被单核细胞和巨噬细胞清除。趋化因子 CCL2 和 CCL5 是将这些免疫细胞招募到肿瘤和组织中的关键介质。本研究的目的是研究 CCL2 和 CCL5 对 NPs 药代动力学（PKs）的影响。与对照小鼠相比，缺乏 CCL2 或 CCL5 的小鼠对聚乙二醇标记的脂质体阿霉素（PLD）的清除率和组织分布发生改变。使用携带 SKOV3 卵巢癌异种移植瘤的小鼠进行的 PK 研究表明，与非肿瘤携带小鼠相比，肿瘤细胞的存在和趋化因子的高表达与 PLD 的清除率显著增加有关。接受 PLD 治疗的复发性上皮性卵巢癌患者的血浆中包裹的脂质体阿霉素的暴露与血浆中 CCL2 和 CCL5 的总暴露呈正相关。这些数据强调了 PLD 与趋化因子之间的相互作用可能在优化 PLD 治疗中发挥重要作用。
纳米颗粒作为药物传递载体在临床环境中得到了广泛的认可。然而，这些新型药物的潜在药代动力学尚未得到真正阐明。在这篇有趣的文章中，作者使用缺乏 CCL2 或 CCL5 的小鼠进行实验，研究了脂质体系统的清除率。他们展示了免疫系统所起的重要作用，并能够为未来的药物传递系统设计提供更好的设计。
