The inherent AIE feature revealed the drug molecular state in cyclodextrin metal-organic framework for enhanced stability and absorption

The amorphous form of a drug can greatly improve the solubility and rates of dissolution for enhancing oral bioavailability. However, amorphous drugs tend to crystallize thus negating their solubility advantages. Here, we use a nanoconfinement strategy to prevent the crystallization of amorphous solids by loading the poorly soluble drug indomethacin (IMC) into a porous gamma-cyclodextrin-based metal-organic framework (CD-MOF). The inherent aggregation-induced emission (AIE) property of IMC was successfully applied as a sensitive fluorescence imaging tool to visualize its molecular state in the solid form. A distinct high-energy, non-aggregated molecular state of IMC in CD-MOF was revealed by the AIE turn-off phenomenon together with other solid-state characterization methods. The IMC@CD-MOF exhibited excellent physical stability even when stored at high temperature or humidity. The high supersaturated drug solutions were immediately generated and maintained during the dissolution of IMC@CD-MOF, resulting in a great enhancement of in vivo bioavailability. The inherent AIE feature of drugs can facilitate the understanding of the structure-property relationship in complex delivery systems, which is essential for the design and optimization of drug carriers with desired stability and biopharmaceutical performance.