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

OBJECTIVES

Antimicrobial resistance emerged as a global challenge owing to limited therapeutic options to control infections. , 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 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 associated surface-infection . First, TC-based nanoemulsions were fabricated by high-pressure homogenization and evaluated for various 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/cm hr), and repressed the CFU of induced-surface infection (≤ 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