Toxicological evaluation of PLA/PVA-naringenin nanoparticles: In vitro and in vivo studies

Abstract

In the present study, the safety profile of the polylactic acid/ polyvinyl alcohol-naringenin (PLA/PVA-Nar) nanoparticles was evaluated. The analysis of cell viability, lactate dehydrogenase (LDH) leakage, and generation of reactive oxygen species (ROS) in the Caco-2 cell line showed no significant changes for the treated cells (5–100 µg/mL) compared to control cells for 24 hr. Moreover, the result of the hemolytic assay confirmed the biocompatibility of the nanoformulation. In acute toxicity, rats were subjected for a single oral exposure to nanoparticles, dose-dependently (5, 50, 300 mg/kg body wt) and monitored for the following 14 days. Whereas for sub-acute toxicity, the animals were dosed at various concentrations (10, 50, 100 mg/kg body wt) for the period of 28 days. The results showed no sign of morbidity and mortality in any of the treated groups in both the toxicological studies. Hematological and serum biochemical parameters and hepatic antioxidant status were unaffected by the treatment when compared to control rats. Furthermore, the histological assay of various organs (brain, liver, kidney, lungs, heart, and intestine) in both studies revealed no hazardous effect at the cellular levels. These results collectively evidenced a lack of toxicity for the nanoformulation over the short and prolonged durations, possibly due to the biocompatibility of the polymers used in the formulation.

Keywords

• Cytotoxicity
• Serum parameters
• Histopathology
• Hematology
• Antioxidant enzymes