非经典结晶路线制备新颖的纳米药物超结构

本课题运用仿生结晶手段制备纳米晶体药物粉体。此结晶体系可以作为模型体系，帮助我们深化对多步结晶机理的认识；同时，将药物结晶成纳米晶体超结构可以有效增加其生物可行性。为实现上述目的，本项目首先利用分子间相互作用和必要的药物筛选实验确立合适的结晶体系。然后，利用多种表征手段采集多步结晶过程中的动力学信息，包括结晶前的前驱体组分变化和纳米晶体的介观组装动力学。最终的溶解度测试和药物释放实验用来支持我们的最初设想-纳米超结构可以作为提高难溶性药物生物可行性的一种简单可行的手段。除了制备高纯度的纳米药物晶体超结构，本研究为前驱体诱导的多步结晶机理提供重要的理论依据和实验支持。考虑到多步结晶机理是最终实现溶液相可控结晶的关键，我们的课题对于溶液相制备功能性超细粉体材料亦有重要的指导意义。

We plan to prepare nanocrystalline drug superstructures via a biomimetic crystallization route. This model crystallization system can help us to deepen our understanding of multistage crystalliation. Simultaneously, preparation of practically insoluble drug molecules into nanocrystalline structures can effectively enhance their bioavailability. To this end, we apply various advanced characterization methods to clarify the underlying mechanism of precursor-involved multistage crystallization. First, we use molecular interactions and necessary drug screening experiments to optimize 1-2 model drug-polyelectrolyte-solvent systems for further investigation. Afterwards, several techniques are applied together to clarify kinetic information, including the formation range of the precursor phases, their compositional change, and the mechanism of precursor transformation into nanocrystalline drug superstructures. Finally, the solubility test and preliminary cell and animal tests support the enhanced drug bioavailability of superstructures compared with their bulk counterparts. In short, we introduce a general and effective biomimetic crystallization route to design nanocrystalline drug superstructures, aiming at enhancing the bioavailability of insoluble drugs. Our experimental study also strongly supports the correctness of precursor-involved multistage crystallization route, which is essential for the controllable crystallization from the solution phase. Therefore, the success of our project sheds light on the success of rational synthesis of functional powder materials.