RESUMEN
Purpose: To investigate the preparation of inclusion complexes of diphenylcyclopropenone (DPCP)/ß-cyclodextrin (ß-CD) derivatives using a three-dimensional (3D) ball mill, and verify the inclusion behavior of the solid dispersion. Additionally, we aimed to investigate the effect of DPCP/ß-CDs complex formation on the spleens of male C57BL/6 mice in terms of anti-inflammatory effects. Methods: The inclusion complexes of DPCP with ß-CD and hydroxypropyl-ß-cyclodextrin (HPßCD) were prepared using a 3D ball mill. Powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to evaluate the solid-state properties. The solubility of the prepared DPCP/ß-CD and HPßCD complexes and the intermolecular interaction between DPCP and ß-CD derivatives in solution were assessed using 1H nuclear magnetic resonance (NMR). Furthermore, the anti-inflammatory effects of DPCPs in the prepared DPCP/CD complexes were investigated using spleens from male C57BL/6 mice, with measurement of interferon gamma (IFN-γ) secretion as an endpoint. Additionally, the protective effects of each drug on NIH-3T3 cells exposed to ultraviolet (UV) irradiation were examined. Results: Solid-state characterization confirmed the formation of inclusion complexes in the 3D ground mixture (3DGM) (DPCP/ß-CD = 1/1) and 3DGM (DPCP/HPßCD = 1/1) complexes through PXRD and IR analysis. The solubility of 3DGM (DPCP/ß-CD = 1/1) and 3DGM (DPCP/HPßCD = 1/1) was 17.5 µg/mL and 58.4 µg/mL, respectively, indicating higher solubility than that of DPCP alone. NMR analysis of 3DGM samples suggested that DPCP/ß-CD and DPCP/HPßCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. Regarding the anti-inflammatory activity of DPCP, 3DGM (DPCP/HPß-CD) showed anti-inflammatory effects at lower doses compared to 3DGM (DPCP/ß-CD) in terms of IFN-γ and NIH-3T3 cells injured by UV irradiation. Conclusion: We successfully formed inclusion complexes of DPCP/ß-CD and DPCP/HPßCD using the 3D ground mixture method. NMR analysis suggested that DPCP/ß-CD and DPCP/HPßCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. The anti-inflammatory activity of DPCP was more pronounced in 3DGM (DPCP/HPßCD) at lower doses compared to that in 3DGM (DPCP/ß-CD), indicating that the HPßCD derivatives were more effective in enhancing the anti-inflammatory properties of DPCP.