Medium-Chain Fatty Acid-Enabled Nanostructured Lipid Carriers for Improved β-carotene Biopharmaceutical Properties and Antioxidant Efficacy

ObjectiveThis study aimed to enhance the in vitro digestion and permeability of β-carotene (BC), a lipophilic antioxidant with therapeutic potential in oxidative stress-related disorders, by developing a nanostructured lipid carrier (NLC) system based on medium-chain fatty acids (MCFAs).SignificanceAlthough BC exhibits strong antioxidant activity, its poor solubility and low gastrointestinal absorption limit clinical use. This study addresses these barriers by formulating a novel medium-chain fatty acid-based NLC using ethanol injection method that improves BC’s solubility, permeability, and bioactivity. The approach offers a scalable oral promising platform for antioxidant therapies targeting chronic diseases linked to oxidative stress.MethodsBC-loaded NLC (BC-NLC) was prepared via ethanol injection and subsequently optimized using a Box–Behnken design. Physicochemical properties, biopharmaceutical performance, and antioxidant effects were evaluated.ResultsThe optimized BC-NLC showed a particle size of 153.9 nm, polydispersity index of 0.29, zeta potential of −14.1 mV, and encapsulation efficiency of 62.0%. In vitro digestion revealed 63-fold and 38-fold increases in BC micellar efficiency in simulated gastric and intestinal fluids, respectively. A 9.1-fold enhancement in intestinal transport was observed. Stability testing confirmed >88% BC retention over 28 days at 5 °C. Antioxidant assays demonstrated ≥2.3-fold higher radical scavenging activity and a 22.7-fold increase in reducing power compared to free BC.ConclusionsThe MCFAs-based BC-NLC effectively overcomes key biopharmaceutical limitations, offering enhanced in vitro digestion, stability, and antioxidant efficacy. It represents a promising oral delivery strategy for oxidative stress-related therapeutic applications.