Moxifloxacin Loaded Nanoemulsions having Tocopheryl Succinate as Integral Component Improves Pharmacokinetics and Enhances Survival in E Coli Induced Complicated Intra-Abdominal Infection

Abstract

In the present work a novel nanoemulsion laden with moxifloxacin has been developed for effective management ofcomplicated Intra-abdominal infections.Moxifloxacin nanoemulsion fabricated using high pressure homogenization was evaluated for various pharmaceutical parameters, pharmacokinetics and pharmacodynamics in rats with E coli induced sepsis. The developed nanoemulsion MONe6 (size 168±28 d.nm and ZP-24.78±0.45mV respectively) was effective for intracellular delivery and sustaining the release of MOX. MONe6 demonstrated improved plasma (AUC MONe6/MOX= 2.38 fold) and tissue pharmacokinetics of MOX (AUC MONe6/MOX= 2.63 and 1.47 times in lung and liver respectively). Calculated PK/PD index correlated well with reduction in bacterial burden in plasma as well as tissues. Enhanced survival on treatment with MONe6 (65.44 %) and as compared to control group (8.22 %) was result of reduction in lipid peroxidation, neutrophil migration and cytokine levels (TNF-α and IL1b) as compared to untreated groups in rat model of E coli induced sepsis.Parenteral nanoemulsions of MOX hold a promising advantage in the therapy of E. coli induced complicated intra-abdominal infectionsand is helpful in the prevention of further complication like septic shock and death.