Membrane Loaded Copper Oleate PEGylated Liposome Combined with Disulfiram for Improving Synergistic Antitumor Effect In Vivo

• Published in: Pharmaceutical research 2018-07, Vol.35 (7), p.147-11, Article 147
• Main Authors: Zhou, Lingli, Yang, Liu, Yang, Chulei, Liu, Yi, Chen, Qiuyue, Pan, Wenli, Cai, Qing, Luo, Lifeng, Liu, Lu, Jiang, Shan, He, Haibing, Zhang, Yu, Yin, Tian, Tang, Xing
• Format: Article
• Language: English
• Subjects: Alcohols; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemical synthesis; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - chemical synthesis; Antitumor activity; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cancer; Carcinoma, Ehrlich Tumor - drug therapy; Carcinoma, Ehrlich Tumor - pathology; Copper; Copper - administration & dosage; Copper - chemistry; Disulfiram; Disulfiram - administration & dosage; Disulfiram - chemical synthesis; Drug delivery systems; Drug Synergism; Efficiency; Hepatoma; Incubation; Injection; Lipids; Liposomes; Liver Neoplasms, Experimental - drug therapy; Liver Neoplasms, Experimental - pathology; Male; Medical Law; Mice; Nanoparticles; NMR; Nuclear magnetic resonance; Oleic Acid - administration & dosage; Oleic Acid - chemical synthesis; Permeability; Pharmaceuticals; Pharmacokinetics; Pharmacology/Toxicology; Pharmacy; Polyethylene glycol; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemical synthesis; Random Allocation; Rats; Rats, Sprague-Dawley; Research Paper; Sodium; Treatment Outcome; Tumor Burden - drug effects; Tumor Burden - physiology; Xenograft Model Antitumor Assays - methods; Xenografts
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-018-2414-5

Purpose This work aims to create a novel Cu 2+ liposome with excellent loading stability and develop synergistic effect with disulfiram (DSF) for the treatment of tumor. Methods Copper oleate was incorporated into the liposome membrane via alcohol injection method in this work. In vitro release test was applied to evaluate the release profile of the liposomes. Pharmacokinetic studies were performed in rats and the antitumor efficacy was assessed in mice bearing hepatoma xenografts. Results The copper oleate liposome (Cu(OI) 2 -L) was formulated and the loading efficiency were more than 85%. TEM images confirmed that the Cu(OI) 2 -L had a spherical morphology with an average diameter of 100 nm. Cu(OI) 2 -L displayed a biphasic release profile, with >70% retained drug over 8 h incubation in PBS at pH 7.4. Pharmacokinetic studies demonstrated that Cu(OI) 2 -L had a prolonged circulation time and increased AUC when compared to the injection of copper oleate solution. The antitumor efficacy test demonstrated an enhanced tumor inhibition rate with the treatment of Cu(OI) 2 -L and DSF nanoparticles, indicating an improved synergistic antitumor effect. Conclusions The Cu(OI) 2 -L was suitable to be employed in combination with disulfiram for tumor treatment and can also open up opportunities for targeted delivery of copper.