Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cancer Lett. 2013 Jul 1;334(2):253-62. doi: 10.1016/j.canlet.2012.08.009. Epub 2012 Aug 16.
The aim of these studies was to develop a novel 2'-behenoyl-paclitaxel (C22-PX) conjugate nanoparticle (NP) formulation for the treatment of metastatic breast cancer. A lipophilic paclitaxel derivative C22-PX was synthesized and incorporated into lipid-based NPs. Free C22-PX and its NP formulation were evaluated in a series of in vitro and in vivo studies. The results demonstrated that C22-PX NPs were much better tolerated and had significantly higher plasma and tumor AUCs compared to Taxol at the maximum tolerated dose (MTD) in a subcutaneous 4T1 mouse mammary carcinoma model. These benefits resulted in significantly improved antitumor efficacy with the NP-based formulation.
这些研究的目的是开发一种新型的 2'-二十二酰基紫杉醇（C22-PX）缀合物纳米颗粒（NP）制剂，用于治疗转移性乳腺癌。合成了一种亲脂性紫杉醇衍生物 C22-PX 并将其纳入脂质 NPs 中。在一系列体外和体内研究中评估了游离 C22-PX 及其 NP 制剂。结果表明，在皮下 4T1 小鼠乳腺癌模型中，与 Taxol 相比，在最大耐受剂量（MTD）下，C22-PX NPs 的耐受性更好，且血浆和肿瘤 AUC 显著更高。这些益处导致基于 NP 的制剂的抗肿瘤疗效显著提高。
