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%)，已知的治疗癌症的药物重新定位是一种全球趋势。我们已经证明，双硫兰(DS)是一种久负盛名的解酒药物，具有良好的抗癌活性，对正常细胞毒性低。然而，DS作为癌症治疗的有效性以前一直受到其生物不稳定性(血液中约4分钟的半衰期)的限制。我们已经证明，通过将DS包裹在特定的纳米颗粒中，我们可以显著改善DS在血液中的半衰期。此外，我们在广泛的癌症类型(基于实验室规模的封装DS产品)中进行了体外和体内试验，产生了令人鼓舞的结果。为了将我们的实验室结果转化为癌症临床，我们提议与江苏省苏州银行谷有限公司中国建立一个合作研究。在这个项目中，苏州银行谷有限公司将开发出GMP质量的纳米胶囊DS，并将其运输到迪舒康有限公司。我们将使用英国(伍尔弗汉普顿大学等地)的实验室设施来检测新开发的纳米DS在动物癌症模型中的体内外抗癌活性。这项建议的目标是验证GMP合格纳米DS的抗癌效果，并在扩大生产和开始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.