Fe2O3-montmorillonite reinforced hydrogel microspheres for pH-responsive co-delivery of l-glutamine and curcumin

The low bioavailability of nutraceuticals, due to chemical instability and non-targeted release, remains a major delivery challenge. To address this, biodegradable core-shell hydrogel microspheres with controllable diameters ranging from 800 to 2850 μm were fabricated via an extrusion method for the co-delivery of hydrophilic and hydrophobic nutraceuticals. These microspheres employ Fe 2 O 3 -loaded montmorillonite (Fe Mt) as the reinforcing scaffold, sodium carboxymethyl cellulose (CMC) as the core, and chitosan (CS) as the shell. They were co-loaded with hydrophilic l -glutamine (L-Gln) and hydrophobic curcumin (Cur) as model nutraceuticals. The incorporation of Fe Mt overcomes the low encapsulation efficiency and mechanical weakness of polymer microspheres. Meanwhile, at Fe Mt contents of 6.00 wt% (for L-Gln) and 5.00 wt% (for Cur) relative to the CMC weight, the encapsulation efficiencies reach up to 75.42% and 63.16%, respectively. The CS shell thickness increases from 10.83 to 16.05 μm as the CS concentration rises from 10.0 to 25.0 g/L. This thickness governs the release kinetics and pH-responsive behavior, wherein the microspheres contract in acidic environments and swell under neutral/alkaline conditions to facilitate targeted delivery in the gastrointestinal tract. In simulated digestion, cumulative release of nutraceuticals from the microspheres was 93.02% for L-Gln and 88.37% for Cur within 12 h. Additionally, the microspheres exhibited good storage stability (ca. 1.03% loss after 45 days). This work presents a highly promising and versatile platform for the co-delivery of hydrophilic and hydrophobic nutraceuticals with controlled release profiles.