Enhanced solubility and biological activities of Flufenamic acid through β-Cyclodextrin derivatives inclusion complexes: A comprehensive study

• Published in: Journal of molecular liquids 2024-05, Vol.402, p.124765, Article 124765
• Main Authors: Mohandoss, Sonaimuthu, Sakthi Velu, Kuppu, Wahab, Rizwan, A. Al-Khedhairy, Abdulaziz, Tamizhselvi, R., Arumugam Napoleon, Ayyakannu, Palanisamy, Subramanian, You, SangGuan, Rok Lee, Yong
• Format: Article
• Language: English
• Subjects: Antibacterial; Anticancer activity; Flufenemic acid; Inclusion complex; Molecular docking; Solubility; β-CDs
• ISSN: 0167-7322
• DOI: 10.1016/j.molliq.2024.124765

[Display omitted] •Inclusion complexes of FNA with various β-CDs were prepared by probe sonication.•The solid β-CDs:FNA inclusion complexes were prepared and characterized by FTIR, XRD, SEM, and TGA-DSC analyses.•Apparent high stability constant of β-CDs:FAN determined by phase solubility study.•The most favorable β-CDs:FNA complexes was confirmed by molecular docking studies.•β-CDs:FNA complexes showed an enhanced antibacterial and anticancer activities. This study explores the formation of inclusion complexes between the solubility enhancement of Flufenamic acid (FNA) and various β-Cyclodextrins (β-CD, Hβ-CD, Mβ-CD, and Sβ-CD) using ultrasonic probe sonication method. The investigation encompasses a multi-faceted analysis, employing UV–Visible, FTIR, XRD, FE-SEM, TGA-DSC techniques and molecular docking studies. The UV–Visible spectra reveal absorption peak shifts and binding constants (Ka) indicate interaction strength, and thermodynamic parameters suggest spontaneous and favorable inclusion processes of β-CDs:FNA. Solid inclusion complexes of β-CDs:FNA were further characterized using FTIR, revealing alterations in functional groups indicative of complex formation. XRD analysis elucidates changes in crystallinity, while FE-SEM provides insights into morphological variations. Thermal stability is assessed through TGA-DSC, demonstrate the impact of inclusion on the complexes stability. Phase solubility diagrams illustrate the improved solubility of FNA in the presence of β-CDs. Mβ-CD:FNA exhibits the highest stability constant (1204 M−1), emphasizing its potential as an effective carrier. The binding energy of Mβ-CD:FNA (−46.72 kcal/mol) was lower than that of β-CD:FNA (−39.03 kcal/mol), Hβ-CD:FNA (−46.40 kcal/mol), and Sβ-CD:FNA (−46.29 kcal/mol), indicating that the hydroxypropyl group substitution enhanced the inclusion ability of β-CDs. Antibacterial activity studies against S. aureus and E. coli highlight enhanced efficacy of inclusion complexes with Mβ-CD:FNA (92.3 ± 0.18 % and 94.2 ± 0.17 %) demonstrating superior antibacterial activity. Cytotoxicity evaluations on HCT-116 cells reveal the safety profile of the β-CDs:FNA inclusion complexes, with Mβ-CD:FNA showing lower toxicity and high cell internalization compared to other formulations. The findings hold promise for applications in drug delivery, antimicrobial packaging, and the broader pharmaceutical and biotechnological fields.