Nanocarrier Mediated Delivery of Gepotidacin: A Novel Triazaacenaphthylene Antibiotic Targeting Drug-Resistant Bacterial Infections

The phenomenon of antimicrobial resistance has become a worldwide health issue, and new approaches to treatment and drug development are needed. Gepotidacin, the first-inclass triazaacenaphthylene antibiotic, has a non-traditional mechanism of action, unlike the fluoroquinolones, by binding gyrase and topoisomerase IV, acting as a non-standard compound. This shows effectiveness against several Gram-positive and Gram-negative bacteria, including MDR strains such as Escherichia coli, Staphylococcus aureus, and Neisseria gonorrhoeae. Nevertheless, its effectiveness is limited by its low solubility, bioavailability, and possible systemic toxicity. Delivery systems using nanocarriers such as liposomes, polymeric nanoparticles, solid lipid NPs, and dendrimers are promising methods for drug delivery, as they can improve solubility, protect the drug against early degradation, and enable targeted delivery via controlled release. Such platforms increase site-specific accumulation, reduce dosing frequency, and reduce off-target effects, thereby maximizing therapeutic effects and patient compliance. In addition to enhanced pharmacokinetics, nanocarrier systems may be designed for active targeting or as stimuli-responsive systems that deliver the drug in response to infection-specific indicators such as pH, enzymes, etc. In preclinical research, it is posited that nanoformulated gepotidacin displays greater antibacterial efficacy and decreased resistance. Nevertheless, despite these advancements, there are still translation issues, such as regulatory, safety, and scale concerns. This review assesses the therapeutic potential of gepotidacin and the benefits of nanocarrier-based delivery in addressing the limitations of current antibiotic treatments.