Evaluation of ceftiofur–PHBV microparticles in rats

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:

• microparticles
• drug delivery
• Salmonella Typhimurium
• rat infection model
• blood parameters

Supplementary material

Figure S1 Increment of weight of rats obtained in the toxicological evaluation at the therapeutic dose.

Abbreviations: PHBV, poly(3-hydroxybutyrate-co-3-hydroxyvalerate); PHBV–Ø, empty microparticles.

Figure S2 Increment of weight of rats obtained in the toxicological evaluation at high doses of microparticles.

Abbreviations: PHBV, poly(3-hydroxybutyrate-co-3-hydroxyvalerate); PHBV–Ø, empty microparticles.

Figure S3 Image showing morphological signs of liver regeneration, without microparticle waste in the ceftiofur–PHBV group.

Notes: Liver sections were stained with H&E. Original magnification 40×.
Abbreviations: H&E, hematoxylin and eosin; PHBV, poly(3-hydroxybutyrate-co-3-hydroxyvalerate).

Table S1 Plasma biochemical parameters obtained in the toxicological evaluation at the therapeutic dose

Table S2 Plasma hematological parameters of rats obtained in the toxicological evaluation at the therapeutic dose

Table S3 Evaluation of plasma coagulation parameters of rats obtained in the toxicological evaluation at the therapeutic dose

Table S4 Plasma biochemical parameters of rats obtained in the toxicological evaluation at high doses of microparticles

Table S5 Plasma hematological parameters of rats obtained in the toxicological evaluation at high doses of microparticles

Table S6 Evaluation of plasma coagulation parameters of rats obtained in the toxicological evaluation at high doses of microparticles

Acknowledgments

The authors acknowledge the financial support of CONICYT under BASAL Grant FB0807 and FONDECYT 1120952. We acknowledge Soung-Jae Bong for his contribution in editing and reviewing this manuscript. CV acknowledges the support of the Grant TPI06 and Becas-Chile fellowship CONICYT-Chile.

Disclosure

The authors report no conflicts of interest in this work.