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

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.