Folic acid-loaded chitosan nanoparticles: Cytotoxicity, acute and sub-acute oral toxicity and bioavailability in Wistar rats

The study aims to develop folic acid-loaded chitosan nanoparticles (FA-Chi-NPs) as the vitamin is sensitive to heat and light and to investigate the safety of FA-Chi-NPs in vitro and in vivo. The prepared formulation showed an average diameter of 191.7 ± 2 nm with a zeta potential of + 52 ± 4 mV and PDI of 0.195 ± 0.03. The encapsulation efficiency was found to be 80%. In vitro cytotoxicity assays revealed that FA-Chi-NPs had no cytotoxic effect on Caco-2 cells. Acute-toxicity and subacute-toxicity of FA-Chi-NPs (0.4, 2, and 4 mg/kg body weight) revealed no mortality, and no gross morphological abnormalities were noticed. There were no dose-dependent toxic effects of free folic acid (FA) and FA-Chi-NPs in haematological, histological, plasma biochemical indices, oxidative stress enzymes, or other parameters when compared to the control group(s). The plasma and tissue levels of FA from FA-Chi-NPs were significantly higher. Results demonstrated enhanced bioavailability of FA from FA-Chi-NPs with no toxicity. Practical applications In the current study, nanoencapsulation is used as a potential approach to enhance folic acid bioavailability. The results showed that encapsulating folic acid in chitosan improved bioavailability with no apparent adverse effects, and thus chitosan could be a promising polymer for safe folic acid delivery.