Hydrogels and nanostructures formed from ciprofloxacin–peptide conjugates

Abstract

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. 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; and (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. 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 the drug can be administered. Nanocarriers that can be used for this purpose include nanoparticles and hydrogels. 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 describes the synthesis of a ciprofloxacin–dehydropeptide conjugate with the aim of forming hydrogels and related nanostructures to be used for the ‘self-delivery’ of antibacterial compounds. We assessed the hydrogelation ability, antibacterial activity, and pharmacokinetic properties. TEM microscopy revealed nanotubes and nanospheres. The conjugate was unable to form hydrogels alone but was able to form hydrogels as the major component of a co-gel with another peptide gelator. Although the conjugate retained antibacterial activity at 400 µM, activity diminished at lower concentrations. Thus, future work should focus on more hydrolysable pro-drug versions of the conjugate or versions where the peptide is connected at an alternate position.