Fast-dissolving antibacterial nanofibers of cyclodextrin/antibiotic inclusion complexes for oral drug delivery

• Published in: Journal of colloid and interface science 2021-03, Vol.585, p.184-194
• Main Authors: Topuz, Fuat, Kilic, Mehmet E., Durgun, Engin, Szekely, Gyorgy
• Format: Article
• Language: English
• Subjects: Antibacterial nanofibers; Antibiotics; Cyclodextrin; Electrospinning; Inclusion complex (IC); Oral drug delivery
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2020.11.072

[Display omitted] •Polymer-free CD@antibiotic inclusion complex nanofibers were prepared by electrospinning.•Bead-fee nanofibers could be produced at two different molar ratios of four antibiotics.•The inclusion-complexation with CD drastically enhanced the water solubility of antibiotics.•The formation of inclusion-complexation was also confirmed by ab initio modeling studies.•The nanofibers rapidly dissolve in artificial saliva, releasing CD@antibiotic complexes. The widespread use of antibacterial electrospun nanofibers is mostly restricted due to their low loading capacity to carry antibiotics and the need to use toxic organic solvents to boost the antibiotic loading capacity. Nanofibers based on natural excipients, such as cyclodextrin (CD)-based nanofibers, can carry larger amounts of antibiotics while achieving better stability via inclusion complexation. Nanofibers were produced by electrospinning and analyzed by electron microscopy to investigate the morphology of fibers. The formation of inclusion-complexation was analyzed by 1H NMR, FTIR, and XRD. Thermal analysis of the fibers was done using TGA. Ab initio modeling studies were done to calculate the complexation energies of antibiotics with CD. A disk-diffusion assay was used to test the antibacterial activity of the fibers. Bead-free antibacterial nanofibers with mean diameters between 340 and 550 nm were produced. The formation of inclusion complexes (IC) between the CD and the antibiotics was confirmed by FTIR and 1H NMR, which was further verified by the disappearance of the crystalline peaks of antibiotics as determined by XRD analysis. Thermal analysis of the nanofibers revealed that the formulations showed good antibiotic encapsulation (45–90%). Ab initio simulations revealed that gentamicin had the highest complexation energy, followed by kanamycin, chloramphenicol, and ampicillin. The antibacterial nanofibers rapidly dissolved in water and artificial saliva, successfully releasing the CD antibiotic complexes. The nanofibers showed high antibacterial activity against Gram-negative Escherichia coli.