Imaging supermolecular interactions of the pharmaceutical-cocrystal of apigenin-nicotinamide binding with serum albumin

In this paper, a new pharmaceutical cocrystal was synthesized using apigenin (AP) and pharmaceutically acceptable conformer nicotinamide (Nico), and the drug delivery between AP-Nico pharmaceutical cocrystal and human serum albumin (HSA) in vivo was studied at atomic scale. The pharmaceutical cocrystal was characterized using Fourier-transform infrared (FTIR) spectroscopy, (1)H NMR spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD), and the self-assembling mechanism was explored. The dissolution and cumulative release in vitro were investigated. Molecular dynamic (MD) simulation combined with fluorescence spectroscopy was used to study the delivery mechanism of AP-Nico to HSA. The results showed that AP was pharmaceutically cocrystallized with Nico, which formed a pharmaceutical cocrystal mainly through hydrogen interaction between the -OH groups of AP and –NH(2) groups of Nico. The solubility of the AP-Nico was 3 times higher than raw AP and the cumulative release rate was 71%. The fluorescence spectroscopy results showed that the AP-Nico pharmaceutical cocrystal bind with Sudlow’s site I inside the HSA molecule with hydrogen-bond interaction as the main force. The Sudlow’s site I of HSA conjugated with AP-Nico explains the conformational changes of HSA in-silico. This study provided a useful reference for synthesizing flavonoid pharmaceutical cocrystal to improve solubility and exploring the interaction mechanism while understanding its delivery mechanism in vivo.