Cationic nanoemulsions bearing ciprofloxacin surf-plexes enhances its therapeutic efficacy in conditions of E. coli induced peritonitis and sepsis.

PURPOSE

Chitosan (CH) coated ciprofloxacin-sodium deoxycholate surfplex (CFn-SDC) loaded nanoemulsion (LE-CH-CFn-SDC) developed in order to improve tissue penetration of the CFn as well as to mop up the endotoxin (Lipopolysaccharides or LPS) released from bacteria during antibiotic treatment.

METHODS

Size and zeta potential was evaluated for nanoemulsions prepared by high-speed homogenization and sonication. Drug analysis in samples was done by HPLC equipped with fluorescence detector. All formulations were evaluated for any change in LPS induced NO and TNF-α release and ROS generation in J774 macrophages. The formulations were also evaluated for in-vitro killing efficiency on E-Coli. The efficacy of formulations in terms of survival and pharmacokinetics and inhibition of induction of cytokines was carried out in E-coli induced peritonitis model in rats. LE-CH-CFn-SDC interacted with LPS both by electrostatic and hydrophobic interactions.

RESULTS

LE-CH-CFn-SDC resulted in reduction of endotoxin release and MIC values for E. coli. LE-CH-CFn-SDC also reduced NO and TNF-α as well as ROS generation by reducing the uptake of LPS in J774 macrophages. LE-CH-CFn-SDC improved CFn pharmacokinetics and tissue distribution, by reducing the bacterial burden, LPS and cytokines (TNF-α and IL-6) thereby improving survival in a rat model of E. coli induced peritonitis.

CONCLUSION

In conclusion, this work highlights the effectiveness of the chitosan-coated nanoemulsion as intracorporeal approach for therapeutic intervention of E. coli induced peritonitis as well as in sepsis.