Nanoprecipitation for controlled formation of rasagaline mesylate (RM) microparticle agents

帕金森病是一种神经退行性疾病，在加拿大每500人中就有1人受到影响。甲磺酸雷沙吉兰（RM）是一种治疗帕金森病的药物。作为亲水性化合物，RM的消除半衰期较短。目前，RM治疗帕金森病的临床应用受到其低生物利用度和每日给药要求的限制。 RM的快速和“突释”释放特性使其对药物递送系统具有挑战性。通过与Hermay Labs Corporation的合作，该项目的总体目标是开发一种生产用于控释系统的RM微粒剂的技术。该项目将采用基于纳米沉淀的方法，通过使用抗溶剂生产RM微粒剂。试剂的物理化学特性（尺寸分布、负载和包封效率）将通过混合物组成和反溶剂的混合动力学来控制。将构建多个组分的溶解度图以指导组成比例的选择。一种新型的2D混合装置将用于确定颗粒的所需性能的组成。RM颗粒剂的形成将在RM溶液和抗溶剂的宽范围的混合速率下诱导，其中存在载体材料以调节RM剂的释放曲线。该项目的潜在成果将是（1）通过纳米沉淀生产RM微粒剂的有效协议;（2）混合条件与RM微粒特性之间的相关性;（3）提高对亲水性化合物的纳米沉淀的理解，一般用于临床药物;（4）专利，会议上的演讲和同行评议期刊上的出版物。四名HQP将接受这一为期两年的项目的培训。NSERC支持的研究活动对于该项目的成功和长期影响至关重要。

Parkinson's disease is a neurodegeneration disorder, affecting 1 in every 500 people in Canada. Rasagiline mesylate (RM) is a drug for treatment of Parkinson's disease. As a hydrophilic compound, RM has a short elimination half-life. Currently the clinical applications of RM for Parkinson's disease treatment are limited by its low bioavailability and the requirement of daily administrations. The quick and 'burst' release profiles of RM make it challenging for drug delivery systems. Through the partnership with Hermay Labs Corporation, the overall goal of the project is to develop a technology for producing RM microparticle agents used in control release systems. The project will employ a nanoprecipitation-based approach for producing RM microparticle agents by using an antisolvent. The physicochemical characteristics (size distribution, loading and encapsulation efficiency) of the agents will be controlled by both mixture composition and mixing dynamics of the antisolvent. The solubility diagrams of multiple components will be constructed to guide the selection of composition ratios. A novel 2D mixing device will be used to determine the composition for desirable properties of the particles. The formation of RM particle agents will be induced in a wide range of mixing rate of the RM solution and the antisolvent with presence of carrier materials to tune the release profile of the RM agents. The potential outcomes of the project will be (1) effective protocols for producing RM microparticle agents by nanoprecipitation; (2) correlations between mixing conditions and the characteristics of RM microparticles; (3) improved understanding of nanoprecipitation for hydrophilic compound in general for clinic medications; (4) Patents, presentations in conferences, and publications in peer-viewed journals. Four HQPs will be trained on this 2-year project. The research activities supported by NSERC is crucial for success and long-term impact of the project.