Vikas Jain1, Prashant Shukla, R Pal, Prabhat Ranjan Mishra. 1. Pharmaceutics Division, Preclinical South PCS 002/011, CSIR-Central Drug Research Institute, Jankipuram Extension Sitapur Road, Lucknow, 226031, India.
Abstract
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.
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.
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