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

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.

• Authors: Vikas Jain, Prashant Shukla, R Pal, Prabhat Ranjan Mishra
• Journal: Pharmaceutical research (Pharm Res) Vol. 31 Issue 10 Pg. 2630-42 (Oct 2014) ISSN: 1573-904X [Electronic] United States
• PMID: 24740243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Cations
• Drug Carriers
• Emulsions
• Lipopolysaccharides
• lipopolysaccharide, E coli O55-B5
• Deoxycholic Acid
• Ciprofloxacin
• Chitosan

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Cations
• Chitosan (chemistry)
• Ciprofloxacin (administration & dosage, pharmacokinetics, therapeutic use)
• Deoxycholic Acid (chemistry)
• Drug Carriers (chemistry)
• Emulsions
• Escherichia coli (drug effects)
• Escherichia coli Infections (drug therapy, microbiology)
• Lipopolysaccharides (metabolism)
• Microbial Sensitivity Tests
• Nanostructures (chemistry)
• Particle Size
• Peritonitis (drug therapy, immunology, microbiology)
• Rats, Wistar
• Sepsis (drug therapy, immunology, microbiology)
• Technology, Pharmaceutical (methods)