Abstract:
Antibiotic resistance is increasing at such an alarming rate that it is now one of the greatest global health
challenges. Undesirable toxic side-effects of the drugs lead to high rates of non-completion of
treatment regimens which in turn leads to the development of drug resistance. We report on the
development of delivery systems that enable antibiotics to be toxic against bacterial cells while sparing
human cells. The broad-spectrum fluoroquinolone antibiotic moxifloxacin (Mox) was successfully
conjugated to poly(ethylene glycol) (PEG) which was further encapsulated into the hydrophobic poly(3-
caprolactone) (PCL) nanoparticles (NPs) with high efficiency, average particle size of 241.8 4 nm and
negative zeta potential. Toxicity against erythrocytes and MDBK cell lines and drug release in human
plasma were evaluated. Hemocompatibility and reduced cytotoxicity of the PEG–Mox and PCL(PEG–
Mox) NPs were demonstrated in comparison to free Mox. Antimicrobial activity was assessed against
drug sensitive and resistant: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and
Klebsiella pneumoniae. The antibacterial activity of Mox was largely maintained after conjugation. Our
data shows that the toxicity of Mox can be effectively attenuated while, in the case of PEG–Mox,
retaining significant antibacterial activity. At the conditions employed in this study for antimicrobial
activity the encapsulated conjugate (PCL(PEG–Mox) NPs) did not demonstrate, conclusively, significant
antibacterial activity. These systems do, however, hold promise if further developed for improved
treatment of bacterial infections.
