Enhanced cellular uptake, transport and oral bioavailability of optimized folic acid-loaded chitosan nanoparticles

Int J Biol Macromol. 2022 May 31:208:596-610. doi: 10.1016/j.ijbiomac.2022.03.042. Epub 2022 Mar 12.

Abstract

Folic acid is a synthetic form of folate widely used for food fortification. However, its bioavailability is limited due to its inherent instability at several conditions. Therefore, a suitable encapsulation system is highly required. In the present study, the fabrication condition for folic acid-loaded chitosan nanoparticle (FA-Chi-NP) was optimized and then subjected to characterization. The optimized formulation had the particle size, zeta potential, and encapsulation efficiency of 180 nm, +52 mV, and 90%, respectively. In vitro release profile showed a controlled release of folic acid from the nanoparticles. Treatment of Caco-2 cells with the formulation showed no adverse effects based on MTT and LDH assays, and also, the cellular uptake was significantly higher after 2 h compared to free folic acid. Further, the oral administration of rats with FA-Chi-NPs (1 mg/kg BW) increased the plasma level of both folic acid (3.2-fold) and its metabolites such as tetrahydrofolate (2.3-fold) and 5-methyltetrahydrofolate (1.6-fold) significantly compared to free folic acid. In a bio-distribution study, duodenum and jejunum were found to be the primary sites for absorption. These findings suggest that chitosan may be a promising carrier for the delivery of folic acid and, therefore, could be exploited for various food applications.

Keywords: Bioavailability; Chitosan; Folic acid; Nanoencapsulation; Response surface methodology; Transport assay.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Caco-2 Cells
  • Chitosan*
  • Drug Carriers
  • Folic Acid
  • Humans
  • Nanoparticles*
  • Particle Size
  • Rats

Substances

  • Drug Carriers
  • Chitosan
  • Folic Acid