Construction of Curcumin and Paclitaxel Co-Loaded Lipid Nano Platform and Evaluation of Its Anti-Hepatoma Activity in vitro and Pharmacokinetics in vivo
Yuxun Wei, Yumeng Wei, Lin Sheng, Jingwen Ma, Zhilian Su, Jie Wen, Lanmei Li, Qiang Jia, Huiyang Liu, Hui Si, Linjin Xiong, Jinglin Chen, Cheng Ju, Ying Zuo, Hongru Yang, Ling Zhao
Abstract
Purpose: The present study aimed to construct a co-loading platform encapsulating curcumin and paclitaxel at ratios of 2:1– 80:1 (w/w) designated “CU-PTX-LNP” and explored the synergistic effects of CU-PTX at different composite proportions on liver cancer cells using the combination index (CI) method. Methods: The CU lipid nanoplatform (CU-LNP) formulation was optimized via single-factor and orthogonal experiments. Various concentrations of PTX were added to the optimal formulation of CU-LNP to generate CU-PTX-LNP and the nanoplatform characterized via differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD), zeta potential, polydispersity index (PDI), and size analyses. The cumulative release, stability, and cytotoxicity of CU-PTX-LNP in LO2, HepG2, and SMMC-7221 cells were assessed in vitro, followed by safety investigation and pharmacokinetic studies in vivo. The anti-tumor activity of CU-PTX-LNP was also evaluated using nude mice. Results: CU-PTX-LNP formulations containing CU:PTX at a range of proportions (2:1– 80:1; w/w) appeared as uniformly dispersed nanosized spherical particles with high entrapment efficiency (EE> 90%), sustained release and long-lasting stability. Data from in vitro cytotoxicity assays showed a decrease in the IC 50 value of PTX of CU-PTX-LNP (by 5.47– 332.7 times in HepG2 and 4.29– 143.21 times in SMMC-7221 cells) compared to free PTX. In vivo, CU-PTX-LNP displayed excellent biosafety, significant anti-tumor benefits and enhanced pharmacokinetic behavior with longer mean residence time (MRT (0-t); CU: 4.31-fold, PTX: 4.61-fold) and half-life (t 1/2z; CU: 1.83-fold, PTX: 2.28-fold) relative to free drugs. Conclusion: The newly designed CU-PTX-LNP platform may serve as a viable technological support system for the successful production of CU-PTX composite preparations. Keywords: curcumin, paclitaxel, lipid nano platform, synergistic effect