ORCID Profile
0000-0002-9409-8090
Current Organisation
University of Adelaide
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Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3NR01789C
Abstract: We have unleashed the potential of NAR and its nanoformulation against acne infections. The results of the ex vivo skin deposition study demonstrate the effectiveness of the developed nano gel as a targeted topical therapy for acne.
Publisher: Diva Enterprises Private Limited
Date: 2016
Publisher: MDPI AG
Date: 10-08-2021
DOI: 10.3390/MICROORGANISMS9081697
Abstract: One approach to combat the increasing incidence of multidrug-resistant (MDR) bacterial pathogens involves repurposing existing compounds with known safety and development pathways as new antibacterial classes with potentially novel mechanisms of action. Here, triclabendazole (TCBZ), a drug originally developed to treat Fasciola hepatica (liver fluke) in sheep and cattle, and later in humans, was evaluated as an antibacterial alone or in combination with sub-inhibitory concentrations of polymyxin B (PMB) against clinical isolates and reference strains of key Gram-positive and Gram-negative bacteria. We show for the first time that in vitro, TCBZ selectively kills methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius at a minimum inhibitory concentration (MIC) range of 2–4 µg/mL, and vancomycin-resistant enterococci at a MIC range of 4–8 µg/mL. TCBZ also inhibited key Gram-negative bacteria in the presence of sub-inhibitory concentrations of PMB, returning MIC90 values of 1 µg/mL for Escherichia coli, 8 µg/mL for Klebsiella pneumoniae, 2 µg/mL for Acinetobacter baumannii and 4 µg/mL for Pseudomonasaeruginosa. Interestingly, TCBZ was found to be bacteriostatic against intracellular S. aureus but bactericidal against intracellular S. pseudintermedius. Additionally, TCBZ’s favourable pharmacokinetic (PK) and pharmacodynamic (PD) profile was further explored by in vivo safety and efficacy studies using a bioluminescent mouse model of S. aureus sepsis. We show that repeated four-hourly oral treatment of mice with 50 mg/kg TCBZ after systemic S. aureus challenge resulted in a significant reduction in S. aureus populations in the blood to 18 h post-infection (compared to untreated mice) but did not clear the bacterial infection from the bloodstream, consistent with in vivo bacteriostatic activity. These results indicate that additional pharmaceutical development of TCBZ may enhance its PK/PD, allowing it to be an appropriate candidate for the treatment of serious MDR bacterial pathogens.
Publisher: Diva Enterprises Private Limited
Date: 2016
Publisher: Diva Enterprises Private Limited
Date: 2016
Publisher: Diva Enterprises Private Limited
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 14-11-2015
Location: Australia
No related grants have been discovered for Bhumika Savaliya.