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. 2025 Aug 18;15(1):30218.
doi: 10.1038/s41598-025-15651-z.

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

Sonaimuthu Mohandoss #  1   2 , Kuppu Sakthi Velu #  3 , Naushad Ahmad  4 , Ramachandran Srinivasan  5 , Prasanta Roy #  3 , Prathap Somu  6
Affiliations

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

Sonaimuthu Mohandoss et al. Sci Rep. .

Abstract

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.

Keywords: Antibacterial, anticancer; Drug-release; Nanofibers; Solubility; β-cyclodextrins.

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Conflict of interest statement

Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
(a) The three-dimensional (3-D) structure of MFA, HCN, MCN and SCN, (b) electrospinning of NFs from ICs of HCN: MFA, MCN: MFA, and SCN: MFA in aqueous solution.
Fig. 2
Fig. 2
Phase solubility diagram of (a) HCN: MFA, (b) MCN: MFA, and (c) SCN: MFA inclusion complex systems in water (n = 3).
Fig. 3
Fig. 3
SEM images of β-CDs and β-CDs: MFA electrospun nanofibers obtained from the aqueous solutions of (a) HCN, (b) MCN, and (c) SCN, (d) HCN: MFA, (e) MCN: MFA, and (f) SCN: MFA ICs. Inset: the photographs of (a) HCN, (b) MCN, (c) SCN, (d) HCN: MFA, (e) MCN: MFA, and (f) SCN: MFA NFs.
Fig. 4
Fig. 4
(a) HCN, (b) MCN, (c) SCN, (d) HCN: MFA (e) MCN: MFA, and (f) SCN: MFA NFs calculated from SEM images (n = 50).
Fig. 5
Fig. 5
The FTIR spectra of (a) HCN (b) MCN (c) SCN (d) MFA, (e) HCN: MFA, (f) MCN: MFA and (g) SCN: MFA NFs.
Fig. 6
Fig. 6
The XRD pattern of (a) HCN (b) MCN (c) SCN (d) MFA, (e) HCN: MFA (f) MCN: MFA and (g) SCN: MFA NFs.
Fig. 7
Fig. 7
(a) TGA thermograms and (b) derivatives of HCN, MCN and SCN, MFA, HCN: MFA, MCN: MFA, and SCN: MFA NFs.
Fig. 8
Fig. 8
UV-Visible spectral solubility of MFA and its ICs of HCN: MFA, MCN: MFA, and SCN: MFA NFs in aqueous solution.
Fig. 9
Fig. 9
Molecular docking studies of 3D structure of MFA, HCN, MCN and SCN, and its ICs of HCN: MFA, MCN: MFA, and SCN: MFA.
Fig. 10
Fig. 10
The cumulative release of MFA and its ICs of (a) HCN: MFA, (b) MCN: MFA, and (c) SCN: MFA NFs in aqueous solution.
Fig. 11
Fig. 11
Antibacterial colony counting method for the typical images of E. coli and S. aureus treated by control (MFA), HCN: MFA NFs, MCN: MFA NFs, and SCN: MFA NFs webs.
Fig. 12
Fig. 12
The anticancer % inhibition versus concentration (µg/mL) bar diagram of (a) MFA, HCN, and HCN: MFA (b) MFA, MCN, and MCN: MFA and (c) MFA, SCN, and SCN: MFA (25–125 µg/mL) on HCT-116 cells after 24 h.
Fig. 13
Fig. 13
Bright-field, DAPI and PI-staining, and merged images of HCT-116 cell lines after incubation for 24 h with HCN: MFA, MCN: MFA, and SCN: MFA NFs webs at 100 µg/mL. (Scale bar ~ 100 μm).
See this image and copyright information in PMC

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