Lingli Zhou1, Liu Yang1, Chulei Yang1, Yi Liu1, Qiuyue Chen2, Wenli Pan3, Qing Cai1, Lifeng Luo1, Lu Liu1, Shan Jiang1, Haibing He1, Yu Zhang1, Tian Yin4, Xing Tang5. 1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. 2. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China. 3. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China. 4. School of Functional food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China. 5. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China. tanglab@126.com.
Abstract
PURPOSE: This work aims to create a novel Cu2+ 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.
PURPOSE: This work aims to create a novel Cu2+ 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.
Authors: Yan Wang; San Zeng; Tien-Min Lin; Lisa Krugner-Higby; Doug Lyman; Dana Steffen; May P Xiong Journal: Pharm Res Date: 2014-05-22 Impact factor: 4.200
Authors: Jai Woong Seo; JooChuan Ang; Lisa M Mahakian; Sarah Tam; Brett Fite; Elizabeth S Ingham; Janine Beyer; John Forsayeth; Krystof S Bankiewicz; Ting Xu; Katherine W Ferrara Journal: J Control Release Date: 2015-10-05 Impact factor: 9.776
Authors: Mohammad Najlah; Ammar Said Suliman; Ibrahim Tolaymat; Sathishkumar Kurusamy; Vinodh Kannappan; Abdelbary M A Elhissi; Weiguang Wang Journal: Pharmaceutics Date: 2019-11-14 Impact factor: 6.321