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

羧甲基淀粉：用于控制释放青蒿素和赤果叶抗疟组合物的生物相容性载体

• 批准号: 455094-2013
• 负责人: Mateescu, MirceaAlexandru
• 金额: $ 5.07万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=575943
• 关键词: Carboxymethyl; starch; biocompatible; carrier; controlled

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.

疟疾是一种传染病，仍然是造成死亡的主要原因之一。2010年，世界卫生组织（世卫组织）估计约有2.19亿例疟疾病例，多达120万人死亡，其中大多数是非洲儿童。 Karici Diagnostics是一家专门从事传染病诊断和治疗的加拿大公司，开发了从植物佩斯基埃拉fuschiaefolia（Pf）中提取的抗疟疾天然制剂。最近，Karici诊断接近青蒿素联合治疗，响应世界卫生组织的需要，并提出了Pf和青蒿素的联合可以提高抗疟活性的假设，特别是对于多药耐药菌株。令人兴奋的体外实验数据往往伴随着令人失望的体内结果，这是因为药物浓度不足，这是由于水溶性差、吸收低和不期望的积累，通常具有有害的副作用。为了克服这些问题，Karici Diagnostics与UQ ± M合作研究了合适的药物载体系统的开发。该系统主要基于淀粉衍生物，用作支持物，以在胃转运期间保护这些生物活性剂并将其转运到吸收部位。该技术概念在于将羧基添加到淀粉链上，以促进紧凑的凝胶状结构的形成，该结构预期在酸性生物介质中具有机械稳定性。该生物材料是药物缓释形式的新材料。由于所提出的抗疟剂是天然的，并且它们的关联是新颖的，因此没有标准方法来测量这些生物活性剂。因此，本项目的挑战不仅涉及合适载体的开发，而且还涉及提出新的分析方法来定量测定单独的活性Pf和青蒿素/Pf组合。除了为合作伙伴公司带来经济效益外，本项目还可以培养高素质的人才和学生，使他们的知识与未来的职业生涯更加相关。