Assessment of acute and subacute toxicity, pharmacokinetics, and biodistribution of eugenol nanoparticles after oral exposure in Wistar rats

Abstract

The present study aimed to assess the safety, toxicity, biodistribution, and pharmacokinetics of eugenol nanoparticles (EONs) following oral administration in Wistar rat models. In the acute toxicity study, the rats were given a fixed dose of 50, 300, and 2000 mg/kg body weight per group orally and screened for 2 weeks after administration. In the subacute study, three different doses (500, 1000, and 2000 mg/kg BW) of EON were administered for 28 days. The results indicated no significant differences in food and water consumption, bodyweight change, hematological and biochemical parameters, relative organ weights, gross findings, or histopathology compared to the control. Additionally, no significant changes were observed in the expression profiles of inflammatory cytokines such as IL-1, IL-6, and TNFα in the plasma, confirming the absence of systemic inflammation. Biodistribution analysis revealed rapid absorption of eugenol and improved bioavailability due to gradual and sustained release, leading to a maximum eugenol concentration of 15.05 μg/mL (Cmax) at approximately 8 h (Tmax) in the blood plasma. Thus, the study provides valuable insights into the utilization of EON for enhancing the stability, solubility, and sustained release of eugenol and highlights its promising safety profile in vivo.

Keywords:

• nanoencapsulation
• eugenol oral exposure
• rat model toxicology
• inflammatory cytokines
• haematological parameters

Acknowledgments

The authors acknowledge Science and Engineering Research Board, Government of India for the research grant (SERB: EEQ/2020/000251) and CSIR-Central Food Technological Research Institute, Mysore, India for the infrastructure and necessary support. Additionally, the authors extend their thanks to the CSIR-CFTRI animal facility. Special appreciation goes to Dr. Anbarasu K from the Department of Biochemistry and Dr. Gopinath M from the Department of Molecular Nutrition at CSIR-CFTRI for their invaluable proofreading of the manuscript and providing constructive suggestions. Pramod G Nagaraju acknowledges the Department of Science and Technology, New Delhi, India, for the DST-INSPIRE fellowship.

Author contributions

Pramod G. Nagaraju: investigation; formal analysis; data curation; writing—original draft.

Ashwini S: investigation; data curation; writing—original draft.

Pooja Rao: review, editing, proofreading the manuscript.

Poornima Priyadarshini: conceptualization; data curation; methodology; writing—review, funding acquisition, and project administration

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.