Carboxymethyl starch: biocompatible carrier for controlled release of artemisinin and peschiera fuschiaefolia antimalaria combination

疟疾是一种传染病，仍然是死亡的主要原因之一。2010年，世界卫生组织(WHO)估计约有2.19亿疟疾病例，多达120万人死亡，其中大部分是非洲儿童。 Karici Diagnostics是一家专门从事传染病诊断和治疗的加拿大公司，该公司开发了从植物Peschiera fuschiaefolia(PF)中提取的抗疟疾天然药物。最近，Karici Diagnotics响应世界卫生组织的需要，接近青蒿素联合疗法，并提出了PF和青蒿素联合治疗可以改善抗疟疾活性的假设，特别是对多药耐药菌株。体外实验数据令人振奋，而体内实验结果往往令人失望，原因是药物浓度不足，水溶性差，吸收低，累积不良且常有不良副作用。为了克服这些问题，Karici诊断公司与UQ？M合作研究了合适的药物载体系统的开发。该系统主要基于一种淀粉衍生物作为载体，用于在胃转运过程中保护这些生物活性物质并将它们输送到吸收部位。该技术的概念在于在淀粉链上添加羧基，以促进形成致密的凝胶状结构，预计在酸性生物介质中机械稳定。这种生物材料是一种新型的药物缓释形式。由于建议的抗疟疾药物是天然的，而且它们之间的联系是新的，所以没有标准的方法来衡量这些生物活性物质。因此，本项目的挑战不仅涉及开发合适的载体，而且还涉及提出新的分析方法来定量测定活性PF和青蒿素/PF的组合。除了为合作公司带来经济利益外，本项目还有助于形成高素质的人才和对学生进行培训，使他们的知识与他们未来的职业生涯更加相关。

Malaria, an infectious disease, is still one of the major causes of mortality. In 2010, the World Health Organization (WHO) has estimated about 219 million cases of malaria and up to 1.2 million deaths, mostly among children in Africa. Karici Diagnostics, a Canadian company specialized in diagnostic and treatment of infectious diseases, developed antimalaria natural agents extracted from plant Peschiera fuschiaefolia (Pf). Recently, Karici Diagnostic approached the Artemisinin combination therapy, answering to a need of the WHO, and advanced the hypothesis that the association of Pf and Artemisinin can improve the antimalarial activity, particularly for multidrug resistant strains. Exciting experimental in vitro data were often followed by disappointing in vivo results because of the insufficient concentration of drug due to poor water solubility, low absorption and undesirable accumulation often with harmful side effects. To overcome these problems, Karici Diagnostic investigated in collaboration with UQÀM the development of suitable drug carrier system. This system is mainly based on a starch derivative used as support to protect these bioactive agents during stomach transit and to transport them at the absorption sites. The technology concept consists in adding carboxyl groups onto the starch chain in order to promote the formation of a compact gel-like structure expected to be mechanically stable in acidic biological medium. This biomaterial is novel for pharmaceutical sustained release forms. Since the proposed antimalarial agents are natural and their association is novel, there are not standard methods to measure these bioactive agents. For this reason, the challenges in the present project concern not only the development of suitable carriers, but also to propose new analytical methods to quantitatively determine the active Pf alone and the Artemisinin/Pf combination. In addition to the economic benefits for the partner company, the present project also enables the formation of highly qualified personel and students training making their knowledge more relevant to their future professional career.