Chitosan-Coated Calcium Alginate Microspheres Loaded with Alpha-Lipoic Acid/2-HP-β-CD Inclusion Complexes Enhance...

Alpha-lipoic acid (ALA) exhibits antioxidant and potential cardiovascular protective effects, but its insufficient stability in acidic environments and poor water solubility limit its oral delivery applications. In this study, the stability of lipoic acid in acidic environments was first evaluated through acid treatment combined with mass spectrometry analysis. Subsequently, 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) and ALA were used to prepare lipoic acid inclusion complexes, which were characterized by phase solubility curves and X-ray diffraction (XRD). The inclusion complexes were further loaded into calcium alginate microspheres, and the properties of the microspheres were evaluated by scanning electron microscopy (SEM), morphological observation under different pH conditions, swelling ratio, and in vitro release experiments. Following acid treatment, the liquid chromatography-mass spectrometry (LC-MS) response of original ALA decreased, suggesting a reduction in detectable original ALA. The inclusion with 2-HP-β-CD significantly improved the solubility of lipoic acid and altered its crystalline characteristics. The inclusion complex-loaded calcium alginate microspheres exhibit a relatively intact microstructure, display distinct morphological changes and swelling behaviors under different pH conditions, and achieve pH-dependent release. This system may serve as a potential oral delivery platform for improving the aqueous dispersibility of ALA and promoting pH-responsive release under simulated intestinal conditions.