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 γ-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.