Improved water dispersibility and photostability in folic acid nanoparticles with transglycosylated naringin using combined processes of wet-milling and freeze-drying.

Abstract

We successfully prepared folic acid (FA) nanoparticles with excellent dispersibility and photostability using a combination of bead milling and freeze-drying with transglycosylated naringin (Naringin-G), a newly developed transglycosylated food additive. Poly-vinyl pyrrolidon (PVP) was used for comparison with Naringin-G. Water dispersibility and photostability of the freeze-dried formulations were assessed. The dispersibility and physicochemical properties of nanoparticle formulations were evaluated using dynamic light scattering, powder X-ray diffraction (PXRD), and small-angle X-ray scattering (SAXS). Results indicated that the median particle size of FA in the slurry bead milled with Naringin-G decreased notably with time and fell below 100 nm after milling for 300 min. Further, FA nanoparticles with Naringin-G were stable without aggregation following re-dispersion of freeze-dried FA formulations in water. Contrarily, the addition of PVP did not prevent the aggregation of FA nanoparticles following re-dispersion of freeze-dried FA formulations. Solid structures of freeze-dried FA formulations with Naringin-G or PVP were assessed using PXRD and SAXS. PXRD patterns of all freeze-dried formulations highlighted broadening and weakening of peaks, indicating a decrease in FA crystallinity following bead milling, regardless of the additive concentration of Naringin-G and PVP. The scattering intensity profiles of FA formulations with PVP dramatically decreased after milling, whereas FA formulations with Naringin-G did not exhibit changes in SAXS patterns. FA formulations with Naringin-G registered faster enhancement in release rate than PVP in pH 1.2 buffer solutions. The release rate of freeze-dried FA formulation with Naringin-G exhibited at least five-fold enhancement when compared to untreated FA. FA formulation with Naringin-G was stable to photodegradation under fluorescent light. Naringin-G prevented photodegradation of FA due to its antioxidant effect and scavenged radicals. These findings indicated that freeze-dried FA formulation with Naringin-G can improve its water-dispersibility and photodegradation due to the effectiveness of Naringin-G as a dispersant and cryoprotectant.