title: Moxifloxacin-loaded nanoemulsions having tocopheryl succinate as the 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 of complicated intra-abdominal infections. Moxifloxacin nanoemulsion fabricated using high pressure homogenization was evaluated for various pharmaceutical parameters, pharmacokinetics (PK) and pharmacodynamics (PD) in rats with E. coli-induced peritonitis and sepsis. The developed nanoemulsion MONe6 (size 168 ± 28 nm and zeta potential (ZP) 24.78 ± 0.45 mV, 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 a reduction in bacterial burden in plasma as well as tissues. Enhanced survival on treatment with MONe6 (65.44%) and as compared to the control group (8.22%) was a result of reduction in lipid peroxidation, neutrophil migration, and cytokine levels (TNF-α and IL6) as compared to untreated groups in the 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 infections and is helpful in the prevention of further complications like septic shock and death.
authors.affiliation: Pharmaceutics Division and ‡Toxicology Division, CSIR-Central Drug Research Institute (Council of Scientific and Industrial Research) , B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP 226031, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Shukla
authors.forename: Ajeet Kumar
authors.initials: AK
authors.lastname: Verma
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dwivedi
authors.forename: Arti
authors.initials: A
authors.lastname: Yadav
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Gupta
authors.forename: Srikanta Kumar
authors.initials: SK
authors.lastname: Rath
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000472:pathogenicity*; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D059413:Intraabdominal Infections / Q000188:drug therapy* / Q000382:microbiology*; D008297:Male; D000077266:Moxifloxacin; D051381:Rats; D018805:Sepsis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D024841:Fluoroquinolones; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000077266:Moxifloxacin
keywords: complicated intra-abdominal infections; cytokines; lipopolysaccharide; moxifloxacin; myeloperoxidase; sepsis