Polymer-free β-cyclodextrins and mefenamic acid inclusion complex nanofibers for enhanced drug solubility and...

In this study, cyclodextrin (CDs) derivatives were used to form mefenamic acid (MFA) supramolecular inclusion complexes (ICs) via a polymer-free electrospinning technique, aiming to improve drug delivery and therapeutic applications. MFA, a non-steroidal anti-inflammatory drug (NSAID), has low water solubility, but its solubility increases when complexed with CDs. Three β-CDs derivatives such as hydroxypropyl β-cyclodextrins (HCN), methyl β-cyclodextrins (MCN), and sulfobutylether β-cyclodextrins (SCN) were used for MFA ICs. Phase solubility studies showed increased MFA solubility with rising amounts of CDs, with stability constants of 337.1, 684.2, and 931.5 M^- 1 for β-CDs: MFA (HCN: MFA, MCN: MFA, and SCN: MFA). SEM analysis of electrospun β-CDs: MFA nanofibers revealed bead-free structures with average diameters of 675 ± 128, 343 ± 92, and 248 ± 42 nm for β-CDs: MFA. FTIR, XRD, and TGA confirmed the characteristics of the nanofibers, and molecular docking studies suggested their stable 3D structures. Drug release studies showed rapid dissolution, with MFA concentrations of 51 ± 2.1 µg/mg, 63 ± 1.3 µg/mg, and 89 ± 1.7 µg/mg released within 60 s, and maximum releases of 82 ± 0.02, 90 ± 0.18, and 98 ± 0.12 µg/mg after 150 s, indicating sustained release. Antibacterial testing against E. coli and S. aureus showed that SCN: MFA NFs had the highest antimicrobial efficiency (99.3 ± 2.89% inhibition against E. coli and 98.3 ± 1.69% inhibition against S. aureus). In vitro cytotoxicity assays on HCT-116 colon cancer cells revealed significant anticancer effects, with inhibition (%) increased to 96.3 ± 2.3%, 91.4 ± 1.7%, and 99.1 ± 1.6% at 125 µg/mL for HCN: MFA, MCN: MFA, and SCN: MFA NFs, respectively. Additionally, fluorescence microscopy (DAPI and PI staining) confirmed enhanced cellular uptake and apoptosis induction in cancer cells after 24 h of incubation with the NFs. These findings highlight their potential as fast-dissolving drug delivery systems, effective antimicrobial agents, and promising candidates for targeted cancer therapy.