Pu Guo1, Chao Pi1, Shijie Zhao1, Shaozhi Fu2, Hongru Yang3, Xiaoli Zheng4, Xiaomei Zhang5, Ling Zhao1, Yumeng Wei1. 1. Department of Pharmaceutics, School of Pharmacy, Southwest Medical University , Luzhou, Sichuan, 646000, P.R. China. 2. Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China. 3. Department of Oncology, Luzhou People's Hospital, Luzhou, Sichuan, 646000, P.R. China. 4. Basic Medical College, Southwest Medical University , Luzhou, Sichuan, 646000, P.R. China. 5. Institute of Medicinal Chemistry of Chinese Medicine, Chongqing Academy of Chinese Materia Medica , Chongqing, 400065, P.R. China.
Abstract
BACKGROUND: A novel nanoemulsion (CU/FU-LN) was developed as an oral 5-fluorouracil and curcumin co-delivery system for synergistic efficacy against liver cancer. METHODS: MTT assay, confocal laser scanning microscope, and H&E staining were utilized to establish the efficacy and safety of CU/FU-LN. RESULTS: The AUC(0-t) of CU/FU-LN was 8.85-fold and 8.59-fold greater than those of CU and FU, respectively. The IC50 of CU/FU-LN was 4.6-fold and 4.9-fold lower than those of FU and CU in HepG2 cells, respectively. In vivo anti-tumor trials, the tumor inhibition rate was significantly elevated by CU/FU-LN (49.29%), compared 24.84% and 4.72% for FU and CU, respectively. Ki-67 immunohistochemical analysis revealed that CU/FU-LN had an obvious anti-proliferation effect. The IC50 of CU/FU-LN in L02 cells was 1.51-fold and 2.60-fold higher than those of CU and FU, respectively. Certain vital organs in the mice of the CU/FU-LN group showed markedly fewer lesions than those of the CU, FU, and CU+FU groups. The CU/FU-LN treatment caused no significant change in mouse body weight relative to the control group (P > 0.05). CONCLUSIONS: We successfully prepared a promising co-delivery platform for the synergistic treatment of liver cancer and it has a comparatively enhanced efficacy and mitigated toxicity.
BACKGROUND: A novel nanoemulsion (CU/FU-LN) was developed as an oral 5-fluorouracil and curcumin co-delivery system for synergistic efficacy against liver cancer. METHODS:MTT assay, confocal laser scanning microscope, and H&E staining were utilized to establish the efficacy and safety of CU/FU-LN. RESULTS: The AUC(0-t) of CU/FU-LN was 8.85-fold and 8.59-fold greater than those of CU and FU, respectively. The IC50 of CU/FU-LN was 4.6-fold and 4.9-fold lower than those of FU and CU in HepG2 cells, respectively. In vivo anti-tumor trials, the tumor inhibition rate was significantly elevated by CU/FU-LN (49.29%), compared 24.84% and 4.72% for FU and CU, respectively. Ki-67 immunohistochemical analysis revealed that CU/FU-LN had an obvious anti-proliferation effect. The IC50 of CU/FU-LN in L02 cells was 1.51-fold and 2.60-fold higher than those of CU and FU, respectively. Certain vital organs in the mice of the CU/FU-LN group showed markedly fewer lesions than those of the CU, FU, and CU+FU groups. The CU/FU-LN treatment caused no significant change in mouse body weight relative to the control group (P > 0.05). CONCLUSIONS: We successfully prepared a promising co-delivery platform for the synergistic treatment of liver cancer and it has a comparatively enhanced efficacy and mitigated toxicity.
Authors: Rabin Neupane; Sai H S Boddu; Mariam Sami Abou-Dahech; Rinda Devi Bachu; David Terrero; R Jayachandra Babu; Amit K Tiwari Journal: Pharmaceutics Date: 2021-06-26 Impact factor: 6.321