Development and characterization of barley starch nanoformulation of folic acid using mild alkali hydrolysis technique

Anaemia, especially folate deficient anaemia, continues to be a worldwide health issue, disproportionately impacting pregnant women, young children, and the elderly. Despite being a conventional treatment strategy, folic acid (FA) supplementation is hindered by its volatility in gastric environments and suboptimal intestinal absorption, which restricts clinical efficacy. This work focuses on preparation and characterization of barley starch-based nanoparticles as an innovative oral delivery vehicle for FA to improve its stability, bioavailability, and sustained release. The optimised formulation (15 min sonication) produced nanoparticles with an average size of 201.9 nm, a polydispersity index of 0.382, and a zeta potential of -29.1 mV, indicating nanoscale homogeneity and colloidal stability. Entrapment efficiency and drug loading were 97.12% and 98.28%, respectively. Spectroscopic (FTIR), thermal (DSC), and crystallographic (XRD) investigations validated molecular connections between FA and starch, with reduced crystallinity, indicating effective encapsulation. <i>In vitro</i> release showed persistent folic acid release (52% over 24 h), aligning most closely with a first-order kinetic model. <i>Ex vivo</i> intestinal permeation experiments demonstrated a 1.92-fold increase in FA permeability from FASN relative to the pure drug solution, whereas stability testing validated exceptional physicochemical stability for three months at both 25 °C/60% RH and 40 °C/75% RH. These data indicate that FASN is a promising oral nanocarrier for folic acid administration, providing protection against stomach degradation, enhancing intestinal absorption, and improving therapeutic efficacy in managing folate shortage.