Evaluation of ceftiofur–PHBV microparticles in rats

Cristian Vilos,^1,3 Luis Constandil,^2,3 Paula I Rodas,^1,3 Mario Cantin,^4,5 Katherine Zepeda,¹ Natalia Herrera,¹ Luis A Velasquez<sup>1,3

1</sup>Center for Integrative Medicine and Innovative Science (CIMIS), Faculty of Medicine, Universidad Andres Bello, Santiago, ²Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Santiago, ³Centro para el Desarrollo de la Nanociencia y Nanotecnología, Universidad de Santiago de Chile, Ecuador, Santiago, ⁴CIMA, Department of Integral Dentistry, Faculty of Dentistry, Universidad de La Frontera, Temuco, ⁵Center of Research in Biomedical Sciences, Universidad Autónoma de Chile, Temuco, Chile

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

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