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

由于从新化合物中开发新药的成本（15亿美元）、时间（15年）和高失败率（高达95%），全球有一种重新定位已知药物用于治疗癌症的趋势。我们已经证明，双硫仑（DS），一个长期建立的抗酒精药物，具有良好的抗癌活性，对正常细胞的低毒性。然而，DS作为一种癌症治疗的有效性先前受到其生物不稳定性（在血液中的半衰期约为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，从而大大提高其在血液中的半衰期。此外，我们已经在广泛的癌症类型中进行了体外和体内试验（基于实验室规模的封装DS产品），并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，我们建议与中国江苏省苏州银谷有限公司建立合作研究。在该项目中，苏州银谷有限公司将按照GMP质量开发纳米封装DS，并将其运输给diulfican有限公司。我们将利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。该提案的目标是验证GMP合格的纳米ds的抗癌功效，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.