Formulation and testing of PLGA-DS as an anti-cancer therapy for FDA and EMA new drug application

由于从新化合物开发新药的成本（15亿美元）、时间（15年）和高失败率（高达95%），全球趋势是重新定位用于治疗癌症的已知药物。双硫仑（DS）是一种历史悠久的抗酒精中毒药物，具有良好的抗癌活性，对正常细胞的毒性较低。然而，DS作为癌症治疗的有效性以前受到其生物不稳定性（在血流中的半衰期约为4分钟）的限制。我们已经证明，我们可以通过将DS封装在某些纳米颗粒中来显著改善DS在血液中的半衰期。此外，我们还在广泛的癌症类型中进行了体外和体内试验（基于实验室规模的包封DS产品），结果令人鼓舞。为了将我们的实验室结果转化为癌症临床，我们建议与中国江苏省苏州银行谷有限公司建立一项合作研究。在该项目中，苏州银谷有限公司将开发GMP质量的纳米胶囊化DS，并将其运输到Disulfican Ltd.。我们将使用英国的实验室设施（伍尔弗汉普顿大学和其他地方），在动物癌症模型中检查新开发的纳米DS的体外和体内抗癌活性。本提案的目的是验证经GMP认证的nano-DS的抗癌疗效，并在扩大生产规模和开展I期临床试验之前提供临床前数据。

Due to the cost ($1.5 billion), time (15 years) and high failure rate (up to 95%) of novel drug development from new compounds, there is a global trend towards the repositioning of known drugs for the treatment of cancer. We have demonstrated that Disulfiram (DS), a long-established anti-alcoholism drug, possesses excellent anticancer activity with low toxicity to normal cells. However, the effectiveness of DS as a cancer treatment has previously been limited by its bio-instability (~4 min half-life in the bloodstream). We have demonstrated that we can substantially improve the half-life of DS in the bloodstream by encapsulating it in certain nano-particles. Furthermore, we have conducted both in vitro and in vivo trials in a wide range of cancer types (based upon laboratory scale encapsulated DS product) that have produced encouraging results. In order to translate our laboratory results into cancer clinic, we propose to set up a collaborative study with Suzhou Bank Valley Ltd in Jiangsu province, China. In this project, Suzhou Bank Valley Ltd will develop nano-encapsulated DS at GMP quality and transport it to Disulfican Ltd. We will use laboratory facilities in the UK (the University of Wolverhampton and elsewhere) to examine the in vitro and in vivo anticancer activity of the newly developed nano-DS in animal cancer models. The goal of this proposal is to verify the anticancer efficacy of the GMP qualified nano-DS and provide preclinical data prior to scaling up manufacturing and embarking upon phase I clinical trials.