J Biomed Nanotechnol. 2020 Aug 1;16(8):1304-1313. doi: 10.1166/jbn.2020.2969.
: Combination chemotherapy of chemo-drugs and natural herbal drugs has been shown to be more advantageous than individual treatment with respect to enhancing cytotoxicity, alleviating toxicity and controlling the development of multidrug resistance (MDR). : The goal of this study is to construct a combined drug delivery system of curcumin liposomes (CUR-LPs) and paclitaxel liposomes (PTX-LPs) to enhance the anticancer activity and reverse the MDR of PTX. : CUR-LPs and PTX-LPs were prepared by solvent evaporation method with optimal formulation composition. MTT assay was used to assess the effect of the combination of CUR-LPs and PTX-LPs treatments on the proliferation of A549/A549-T cells. In addition, the pharmacokinetic behaviors of the combination treatments were evaluated by HPLC. Results : The mixed liposomes were found to have negative zeta-potential (-17.91 ± 1.21 mV) and relatively uniform particle size (105.88 ± 3.19 nm) with a low polydispersity index (0.21 ± 0.016). IC of PTX for combination of CUR-LPs and PTX-LPs decreased in the range of 1.47-2.9 times and 1.59-2.5 times compared to the free-drug counterparts in A549 and A549-T cells, respectively. Superior cytotoxicity and higher synergy (CI 0.4) were observed for the combination treatment with ratio of 40:1 (CUR-LPs:PTX-LPs) compared with the free-drug counterparts in both cell lines tested. Following intravenous administration in rats, liposomes presented higher bioavailability (CUR-LPs: 9.02 fold; PTX-LPs: 7.32 fold) compared to free drugs. Co-administration did not alter the respective pharmacokinetic behaviors. : Overall, the present study presents a promising strategy for the development of compound formulations of CUR and PTX.
联合化疗药物和天然草药药物已被证明比单独治疗更有利，因为它可以增强细胞毒性、减轻毒性和控制多药耐药性（MDR）的发展。本研究的目的是构建姜黄素脂质体（CUR-LPs）和紫杉醇脂质体（PTX-LPs）的联合药物递送系统，以增强 PTX 的抗癌活性并逆转其多药耐药性。采用溶剂蒸发法制备 CUR-LPs 和 PTX-LPs，优化配方组成。MTT 法评估 CUR-LPs 和 PTX-LPs 联合治疗对 A549/A549-T 细胞增殖的影响。此外，通过 HPLC 评估联合治疗的药代动力学行为。结果表明，混合脂质体具有负的 Zeta 电位（-17.91 ± 1.21 mV）和相对均匀的粒径（105.88 ± 3.19nm），具有较低的多分散指数（0.21 ± 0.016）。与游离药物相比，CUR-LPs 和 PTX-LPs 联合治疗的 PTX 的 IC 在 A549 和 A549-T 细胞中分别降低了 1.47-2.9 倍和 1.59-2.5 倍。与游离药物相比，在两种细胞系中，CUR-LPs：PTX-LPs 比值为 40:1 时，联合治疗具有更好的细胞毒性和更高的协同作用（CI 0.4）。与游离药物相比，脂质体在大鼠体内具有更高的生物利用度（CUR-LPs：9.02 倍；PTX-LPs：7.32 倍）。联合给药不会改变各自的药代动力学行为。总之，本研究为 CUR 和 PTX 的复方制剂的开发提供了一种有前景的策略。
