Reference - Detail
| RRC ID | 81842 |
|---|---|
| Author | Inoue Y, Yoshino K, Kudo S, Kodama N, Moteki H, Kimura M. |
| Title | Preparation, solubility, and anti-inflammatory effects of a complex of diphenylcyclopropenone/β-cyclodextrin derivatives as the treatment of alopecia areata. |
| Journal | J Pharm Pharm Sci |
| Abstract |
PURPOSE: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. METHODS: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. RESULTS: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. CONCLUSION: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. |
| Volume | 27 |
| Pages | 13230 |
| Published | 2024-1-1 |
| DOI | 10.3389/jpps.2024.13230 |
| PII | 13230 |
| PMID | 39193564 |
| PMC | PMC11348807 |
| MeSH | 2-Hydroxypropyl-beta-cyclodextrin / chemistry 2-Hydroxypropyl-beta-cyclodextrin / pharmacology Alopecia Areata* / drug therapy Animals Anti-Inflammatory Agents* / chemistry Anti-Inflammatory Agents* / pharmacology Cyclopropanes* / administration & dosage Cyclopropanes* / chemistry Cyclopropanes* / pharmacology Male Mice Mice, Inbred C57BL* Solubility* Spleen / drug effects beta-Cyclodextrins* / chemistry beta-Cyclodextrins* / pharmacology |
| Resource | |
| Human and Animal Cells | NIH3T3/14-1(RCB0056) |