Laboratory of Nutri-Pharmacotherapeutics Management, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Japan.
Laboratory of Clinical Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Japan.
J Pharm Pharm Sci. 2024 Aug 13;27:13230. doi: 10.3389/jpps.2024.13230. eCollection 2024.
To investigate the preparation of inclusion complexes of diphenylcyclopropenone (DPCP)/β-cyclodextrin (β-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/β-CDs complex formation on the spleens of male C57BL/6 mice in terms of anti-inflammatory effects.
The inclusion complexes of DPCP with β-CD and hydroxypropyl-β-cyclodextrin (HPβCD) 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/β-CD and HPβCD complexes and the intermolecular interaction between DPCP and β-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.
Solid-state characterization confirmed the formation of inclusion complexes in the 3D ground mixture (3DGM) (DPCP/β-CD = 1/1) and 3DGM (DPCP/HPβCD = 1/1) complexes through PXRD and IR analysis. The solubility of 3DGM (DPCP/β-CD = 1/1) and 3DGM (DPCP/HPβCD = 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/β-CD and DPCP/HPβCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. Regarding the anti-inflammatory activity of DPCP, 3DGM (DPCP/HPβ-CD) showed anti-inflammatory effects at lower doses compared to 3DGM (DPCP/β-CD) in terms of IFN-γ and NIH-3T3 cells injured by UV irradiation.
We successfully formed inclusion complexes of DPCP/β-CD and DPCP/HPβCD using the 3D ground mixture method. NMR analysis suggested that DPCP/β-CD and DPCP/HPβCD 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/HPβCD) at lower doses compared to that in 3DGM (DPCP/β-CD), indicating that the HPβCD derivatives were more effective in enhancing the anti-inflammatory properties of DPCP.
研究使用三维（3D）球磨机制备二苯环丙烯酮（DPCP）/β-环糊精（β-CD）衍生物的包合物，并验证固体分散体的包合行为。此外，我们旨在研究 DPCP/β-CDs 复合物形成对雄性 C57BL/6 小鼠脾脏的抗炎作用的影响。
使用 3D 球磨机制备 DPCP 与β-CD 和羟丙基-β-环糊精（HPβCD）的包合物。粉末 X 射线衍射（PXRD）和傅里叶变换红外光谱（FT-IR）用于评估固态性质。使用 1H 核磁共振（NMR）评估制备的 DPCP/β-CD 和 HPβCD 复合物的溶解度以及 DPCP 和β-CD 衍生物在溶液中的分子间相互作用。此外，使用雄性 C57BL/6 小鼠的脾脏研究 DPCP 在制备的 DPCP/CD 复合物中的抗炎作用，以干扰素γ（IFN-γ）分泌作为终点。此外，还研究了每种药物对暴露于紫外线（UV）照射的 NIH-3T3 细胞的保护作用。
固态表征通过 PXRD 和 IR 分析证实了 3D 地面混合物（3DGM）（DPCP/β-CD=1/1）和 3DGM（DPCP/HPβCD=1/1）复合物中包合物的形成。3DGM（DPCP/β-CD=1/1）和 3DGM（DPCP/HPβCD=1/1）的溶解度分别为 17.5μg/mL 和 58.4μg/mL，表明溶解度高于单独的 DPCP。3DGM 样品的 NMR 分析表明，DPCP/β-CD 和 DPCP/HPβCD 以 1/1 的摩尔比形成包合物，但包合方式不同。关于 DPCP 的抗炎活性，与 3DGM（DPCP/β-CD）相比，3DGM（DPCP/HPβCD）在较低剂量下表现出抗炎作用，这体现在 IFN-γ 和 NIH-3T3 细胞因 UV 照射而受伤的情况下。
我们成功地使用 3D 地面混合物法形成了 DPCP/β-CD 和 DPCP/HPβCD 的包合物。NMR 分析表明，DPCP/β-CD 和 DPCP/HPβCD 以 1/1 的摩尔比形成包合物，但包合方式不同。与 3DGM（DPCP/β-CD）相比，3DGM（DPCP/HPβCD）在较低剂量下的 DPCP 抗炎活性更强，表明 HPβCD 衍生物在增强 DPCP 的抗炎特性方面更有效。
