Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic that possesses potent activity against both Gram-positive and Gram-negative bacteria and is used to treat many infections.1 Despite its widespread use, ciprofloxacin is associated with side effects, which might be reduced by improving its pharmacokinetic properties. The chemical structure of ciprofloxacin is the source of some of its limitations, which include: 1) Poor membrane permeability, due to lipophobicity caused by the presence of polar groups; 2) poor transportation and absorption, due to poor water solubility caused by the flat aromatic structure.
Previous methods for improving the pharmacokinetic properties of ciprofloxacin have involved the synthesis of conjugates.2,3 Issues related to poor membrane permeability, transportation and absorption of drugs can also be improved by employing nanocarriers and nanomaterials. Encapsulation within nanocarriers allows targeted drug delivery, and reduced side effects as lower doses of drug can be administered. Nanocarriers that can be used for this purpose include nanoparticles and hydrogels.4,5 Our research group is interested in supramolecular hydrogels as drug delivery systems. Short amphiphilic peptides are often able to form hydrogels through self-assembly.
This present work desribes the synthesis of a panel of ciprofloxacin–peptide conjugates with the aim of forming hydrogels and related nanostructures to be used for the ‘self-delivery’ of antibacterial compounds. We assessed their hydrogelation ability, antibacterial activity and pharmacokinetic properties. Analysis by TEM microscopy revealed spherical nanostructures. The conjugates were unable to form hydrogels alone, but were able to form strong hydrogels with unique properties as co-gels with other peptide hydrogelators. The ciprofloxacin–peptide conjugates retained antibacterial activity. The drug release profile of ciprofloxacin from within the co-gels was also studied.
2. ChemistrySelect, 2016, 6, 1132. https://doi.org/10.1002/slct.201600091
3. Medicinal Chemistry, 2010, 6, 51. http://dx.doi.org/10.2174/157340610791321442
4. Nanomaterials, 2021, 11, 704. https://doi.org/10.3390/nano11030704
5. Soft Matter, 2022, 18, 3955. https://doi.org/10.1039/D2SM00121G