Evaluation of ceftiofur-PHBV microparticles in rats

Drug Des Devel Ther. 2014 May 29:8:651-66. doi: 10.2147/DDDT.S60444. eCollection 2014.

Abstract

Despite the high number of antibiotics used for the treatment of infectious disease in animals, the development of slow release formulations presents a significant challenge, particularly in using novel biomaterials with low cost. In this report, we studied the pharmacokinetics, toxicity, and therapeutic activity of ceftiofur-PHBV (ceftiofur-poly(3-hydroxybutyrate-co-3-hydroxyvalerate)) in rats. The pharmacokinetic study demonstrated a sustained release of ceftiofur into the bloodstream, with detectable levels over the minimum inhibitory concentration for at least 17 days after a single intramuscular injection of ceftiofur-PHBV (10 mg/kg weight). In addition, the toxicological evaluation of biochemical, hematological, and coagulation blood parameters at the therapeutic dose demonstrated the safety of ceftiofur-PHBV, with no adverse effects. In addition, ceftiofur-PHBV exhibited a therapeutic effect for a longer time period than the nonencapsulated ceftiofur in rats challenged with Salmonella Typhimurium. The slow release of ceftiofur from the ceftiofur-PHBV, its low toxicity in the blood parameters evaluated, and the efficacy in the rats infected with Salmonella Typhimurium make ceftiofur-PHBV a strong candidate for biotechnological applications in the veterinary industry.

Keywords: Salmonella Typhimurium; blood parameters; drug delivery; microparticles; rat infection model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cephalosporins / administration & dosage
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Erythrocytes / drug effects
  • Injections, Intramuscular
  • Male
  • Microbial Sensitivity Tests
  • Polyesters / administration & dosage
  • Polyesters / pharmacology
  • Polyesters / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Salmonella Infections / drug therapy*
  • Salmonella Infections / microbiology
  • Salmonella typhimurium / drug effects
  • Structure-Activity Relationship

Substances

  • Cephalosporins
  • Polyesters
  • poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate)
  • ceftiofur