Thiazole derivative based topical nanoemulgel for inhibition of bacterial virulence in surface infections

Document Type : Original Article

Authors

1 Department of Pharmaceutical Science, SHALOM Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences (SHUATS), Naini, Prayagraj, India

2 I.T.S College of Pharmacy, Murad Nagar, Ghaziabad, U.P. (201206), India

3 Regional Centre for Biotechnology, Department of Biotechnology (DBT), Faridabad, Haryana, 121001, India. 411040

Abstract

Objective(s): Antimicrobial resistance emerged as a global challenge owing to limited therapeutic options to control infections. Pseudomonas aeruginosa, an MDR pathogen already developed resistance against many conventional antibiotics. An “anti-virulence strategy” that targets bacterial virulence rather than growth proves effective against drug-resistant pathogens. 
Materials and Methods: Here, we used a structure-based drug design approach to identify lead molecules using the LasR receptor protein of P. aeruginosa as a target responsible for virulence production in this bacterium. From the identified hits, we developed lead-based nanoformulation and investigated its effectiveness for treating the P. aeruginosa associated surface-infection in-vivo. First, TC-based nanoemulsions were fabricated by high-pressure homogenization and evaluated for various in vitro parameters. The optimized nanoemulsions were thereby utilized to prepare NEG.
Results: The nanoemulsion (F3) exhibited low droplet size (51.04±1.88 nm), PDI (0.065±1.14), and negative zeta potential (-33.65±0.82 mV). In animals, topical application of NEG-3 demonstrated significant improvement on skin permeability (459±10.17 µg), drug influx (18.99±0.76 μg/cm2 hr), and repressed the CFU of P. aeruginosa induced-surface infection (P≤0.001). The histology of rat skin demonstrated a significant effect for groups treated with TC-based NEGs as compared with a negative control group, whereas no significant effect was seen on rat liver indicating low systemic exposure to the drug. Also, NEG3 showed no significant changes under different stability conditions after 3 months.
Conclusion: TC-based NEGs open up the possibility of a more effective way to combat serious surface infections caused by P. aeruginosa.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 25, Issue 3
March 2022
Pages 352-363

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