Abstract
Background: The emergence of drug resistance and limited development of newer antibacterials is of serious concern. Furthermore, the invention of novel composites, specifically those that can efficiently traverse the blood-brain barrier to access the central nervous system are scarce. Nanotechnology is a strategy that can be employed to enhance drug delivery and efficacy against infections due to multi-drug resistant bacteria. Given challenges of drug discovery and development, drug repurposing is a useful avenue. Hence, it is logical to test antibacterial effects of currently marketed drugs for central nervous system (CNS) diseases.
Methods: Here, we selected drugs that are clinically used for CNS disorders and are effective in penetrating the blood-brain barrier. These were phenobarbitone, phenytoin, and levetiracetam. These drugs were tested in their available formulation and following conjugation with silver nanoparticles against neuropathogenic Escherichia coli and methicillin-resistant Staphylococcus aureus. The drugs were successfully conjugated with silver and formulations were verified using ultraviolet-visible spectrophotometry, atomic force microscopy, and Fourier transformation infrared spectroscopy.
Results: The results showed that selective drug-conjugated silver nanoparticles and silver nanoparticles displayed bactericidal effects when compared to the drugs alone. Of note, drug-conjugated silver nanoparticles inhibited bacterial-mediated host cell death. When incubated with human cells, both the drugs and drug-conjugated silver nanoparticles showed minimal toxic effects.
Conclusions: These findings suggest that drug repurposing is a viable approach and currently available CNS drugs should be tested following conjugation with nanoparticles against CNS pathogens, as they are clinically approved with established pharmacokinetics and are able to permeate the blood-brain barrier, suggesting their potential translational value.
Methods: Here, we selected drugs that are clinically used for CNS disorders and are effective in penetrating the blood-brain barrier. These were phenobarbitone, phenytoin, and levetiracetam. These drugs were tested in their available formulation and following conjugation with silver nanoparticles against neuropathogenic Escherichia coli and methicillin-resistant Staphylococcus aureus. The drugs were successfully conjugated with silver and formulations were verified using ultraviolet-visible spectrophotometry, atomic force microscopy, and Fourier transformation infrared spectroscopy.
Results: The results showed that selective drug-conjugated silver nanoparticles and silver nanoparticles displayed bactericidal effects when compared to the drugs alone. Of note, drug-conjugated silver nanoparticles inhibited bacterial-mediated host cell death. When incubated with human cells, both the drugs and drug-conjugated silver nanoparticles showed minimal toxic effects.
Conclusions: These findings suggest that drug repurposing is a viable approach and currently available CNS drugs should be tested following conjugation with nanoparticles against CNS pathogens, as they are clinically approved with established pharmacokinetics and are able to permeate the blood-brain barrier, suggesting their potential translational value.
| Original language | English |
|---|---|
| Pages (from-to) | 1-7 |
| Number of pages | 7 |
| Journal | New Zealand Journal of Medical Laboratory Science |
| Volume | 74 |
| Issue number | 3 |
| Publication status | Published - 1 Nov 2020 |