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

• Published in: International journal of biological macromolecules 2022-05, Vol.208, p.596-610
• Main Authors: Fathima, Eram, Nallamuthu, Ilaiyaraja, Anand, T, Naika, Mahadeva, Khanum, Farhath
• Format: Article
• Language: English
• Subjects: Bioavailability; Chitosan; Folic acid; Nanoencapsulation; Response surface methodology; Transport assay
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.03.042

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. [Display omitted] •Response surface methodology was used to optimize the preparation of nanoparticles.•Folic acid was successfully loaded into chitosan by ionic gelation method.•The prepared nanoparticles showed better stability and controlled release.•FA-Chi-NPs remarkably enhanced cellular uptake of folic acid.•Nanoencapsulation increased relative oral bioavailability of folic acid.