Pharmaceutical Research

, Volume 31, Issue 10, pp 2630–2642 | Cite as

Cationic Nanoemulsions Bearing Ciprofloxacin Surf-Plexes Enhances Its Therapeutic Efficacy in Conditions of E. coli Induced Peritonitis and Sepsis

  • Vikas Jain
  • Prashant Shukla
  • R. Pal
  • Prabhat Ranjan Mishra
Research Paper
First Online:
Received:
Accepted:

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.

KEY WORDS

cationic nanoemulsion endotoxin peritonitis ROS sepsis tissue injury 

ABBREVIATIONS

CFn

Ciprofloxacin

CFn-SDC

Ciprofloxacin-sodium deoxycholate surfplex

CFU

Colony forming units

CH

Chitosan

DCF

Carboxy 2,7-dichlorofluorescein

DLS

Dynamic light scattering

DMEM

Dulbecco’s modified eagle medium

EE

Entrapment efficiency

FBS

Fetal bovine serum

FITC DCFH-DA

Carboxy 2,7-dichlorofluorescein diacetate

IL-6

Interleukin-6

LPS

Lipopolysaccharide

MIC

Minimum inhibitory concentration

mV

Milli-volt

NO

Nitric oxide

PF-68

Pluronic F-68

ROS

Reactive oxygen species

SI

Stimulatory index

TLR-4

Toll like receptor-4

TNF-α

Tissue necrosis factor alpha

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Notes

Funding

The author acknowledges the funding received by ICMR (under Adhoc project) and Vikas Jain is acknowledges the support (as senior research fellowship) received from CSIR. New Delhi, India. The author also acknowledges funding from CSIR network project UNDO (BSC 0103).

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Vikas Jain
    • 1
  • Prashant Shukla
    • 1
  • R. Pal
    • 1
  • Prabhat Ranjan Mishra
    • 1
  1. 1.Pharmaceutics Division, Preclinical South PCS 002/011CSIR-Central Drug Research InstituteLucknowIndia

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