Cisplatin and curcumin co-loaded nano-liposomes for the treatment of hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) continues to be a leading cause of cancer related death in the world. Conventional chemotherapeutic agents such as cisplatin (CDDP) have an unsatisfactory efficacy on HCC due to the poor response, severe toxicity and drug resistance. Curcumin (CUR) could improve the chemosensitivity of HCC to chemotherapy drugs by regulating a variety of signaling pathways. Herein, we describe a combination strategy using co-loaded liposomes to effectively deliver and release CDDP and curcumin (CUR) to HCC for overcoming the unsatisfactory clinical outcome of CDDP monotherapy. In the study, CDDP and CUR co-loaded liposomes (CDDP/CUR-Lip) were prepared by a reverse microemulsion and film dispersion method and their average particle size 294.6 ± 14.8 nm with uniform size distribution. In vitro study showed that the nano sized CDDP/CUR-Lip could synchronously release both CDDP and CUR to achieve the synergistic effect against HCC cells based on the optimal ratio (1:8) of both drugs. Compared with free drug or encapsulated mono-drug therapy, CDDP/CUR-Lip demonstrated the higher anti-tumor activity in vitro against HepG2 cells with the IC50 of 0.62 μM. In addition, CDDP/CUR-Lip also increased intracellular ROS level during the HCC cells treatment. Furthermore, compared with single drug formulation, CDDP/CUR-Lip showed the elongated retention time (t1/2 = 2.38 h) and improved antitumor effect in both mouse hepatoma H22 and human HCC HepG2 xenograft models with reduced side effects. In conclusion, CDDP/CUR-Lip provide an attractive and potential strategy to attain synergistic effect of CDDP and CUR for the treatment of HCC.

• Authors: Yao Cheng, Pengxuan Zhao, Shuangping Wu, Tan Yang, Yan Chen, Xiaojuan Zhang, Chuanchuan He, Chao Zheng, Kelin Li, Xiang Ma, Guangya Xiang
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 545 Issue 1-2 Pg. 261-273 (Jul 10 2018) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 29730175 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Lipids
• Liposomes
• Reactive Oxygen Species
• Curcumin
• Cisplatin

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, chemistry, pharmacokinetics)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cisplatin (administration & dosage, chemistry, pharmacokinetics)
• Curcumin (administration & dosage, chemistry, pharmacokinetics)
• Dose-Response Relationship, Drug
• Drug Compounding
• Drug Liberation
• Drug Synergism
• Female
• Hep G2 Cells
• Humans
• Lipids (chemistry)
• Liposomes
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles
• Nanotechnology
• Oxidative Stress (drug effects)
• Particle Size
• Reactive Oxygen Species (metabolism)
• Technology, Pharmaceutical (methods)
• Tissue Distribution
• Xenograft Model Antitumor Assays