基于尺寸效应与界面效应研究吸附水对介孔载药体系的影响

Compared to their crystalline form, amorphous drugs can effectively enhance the solubility and dissolution of poorly water-soluble drugs. From the thermodynamic perspective, amorphous materials are metastable and tend to revert back to the more stable crystalline forms. Therefore, it is crucial to maintain the physical stability of amorphous drugs. Due to the nanoconfinement effect, loading drugs into the mesoporous materials can be one of effective techniques to inhibit the crystallization of amorphous drugs. Dimensional and interfacial factors both influence the molecular mobility of amorphous drugs in the nanopore matrices, and ultimately decide their physical stability and release behaviors. Adsorbed water has been reported to prominently affect the release behavior of amorphous drug in the nanopore matrices and effectively overcome the problem of incomplete release of drugs from mesoporous systems. However, mechanisms for the effect of water on mesoporous formulations still lack fully understanding. In this proposal, the effect of absorbed water will be further investigated from the perspective of dimensional and interfacial effects. With the aid of thermodynamic and kinetic measurement techniques, the effects of absorbed water on the molecular mobility of amorphous drugs as well as the interactions between drug molecules and pore walls can be systematically investigated. This work further demonstrates whether effect of adsorbed water exhibit strong dependence upon the dimension and wall structure of nanopores in mesoporous systems. This work is relevant for understanding the effects of adsorbed water on the physical stability and release behaviors of amorphous drugs in mesoporous systems. In summary, the goal of this work is to achieve the controlled-release by utilizing adsorbed water molecule and rationally design the mesoporous materials-based drug delivery systems.

相比晶态形式，药物无定形态可有效改善难溶性药物的溶解度和溶出。但无定形态处于热力学非稳态，易于发生结晶。如何有效维持其物理稳定性极为重要。在众多技术手段中，利用介孔材料纳米孔道的受限效应可有效抑制无定形药物结晶。尺寸效应和界面效应共同影响纳米孔道中药物分子运动，并最终决定其物理稳定性和药物释放。研究表明纳米孔道中吸附水亦可显著影响纳米孔道药物释放，并有效解决纳米孔道药物非完全释放的问题。但水对介孔载药体系影响的内在机制尚未完全清楚。本项目拟从尺寸效应和界面效应的角度深入研究水对介孔载药体系的影响，结合热力学和动力学的手段系统研究水对纳米孔道中的药物分子运动以及药物-孔道壁相互作用的影响，并阐明吸附水作用机制的孔道尺寸和孔道壁结构依赖性。有助于进一步揭示吸附水对纳米孔道中药物物理稳定性及释放影响的内在机制，为合理利用水分子本身的性质来最终实现药物的控释以及理性设计介孔载药体系提供理论指导。

相比晶态形式，药物无定形态可有效改善难溶性药物的溶解度和溶出。但无定形态处于热力学非稳态，易于发生结晶。如何有效维持其物理稳定性极为重要。本项目研究包括介孔载药体系在内的多种无定形药物制剂的结晶动力学和物理稳定性。本项目围绕无定形药物物理稳定性开展研究，并系统阐述了表面效应和尺寸效应对无定形药物结晶的影响，在研究中引入分子运动这一关键因素，初步构建了分子运动、表面效应等因素在内的无定形药物制剂物理稳定性模型。 此外，本项目还研究了界面效应对无定形药物溶出的影响及其内在机制探讨。本项目有助于进一步加深对无定形药物制剂物理稳定性和溶出的机制研究，为无定形药物制备、贮存、使用提供理论指导。