Chitosan-Coated Calcium Alginate Microspheres Loaded with Alpha-Lipoic Acid/2-HP-β-CD Inclusion Complexes Enhance Aqueous Solubility and Enable pH-Responsive Intestinal Release
- 1School of Basic Medicine, Qingdao University, Qingdao 266071, China
- 2NHC Key Laboratory of Cardiopulmonary Rehabilitation and Functional Recovery, School of Life Sciences and Health, University of Health and Rehabilitation Sciences, Qingdao 266113, China
- 3School of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China
Abstract
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.
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BibTeX
@article{cui2026chitosancoated,
title = {{Chitosan-Coated Calcium Alginate Microspheres Loaded with Alpha-Lipoic Acid/2-HP-β-CD Inclusion Complexes Enhance Aqueous Solubility and Enable pH-Responsive Intestinal Release}},
author = {Yu Cui and Shiya Huang and Yeming Fu and Zihao Zhou and Xiaowen Sun and Huadong Liu and Yuhong Lai},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208998},
url = {https://www.mdpi.com/1422-0067/27/20/8998},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chitosan-Coated Calcium Alginate Microspheres Loaded with Alpha-Lipoic Acid/2-HP-β-CD Inclusion Complexes Enhance Aqueous Solubility and Enable pH-Responsive Intestinal Release
AU - Yu Cui
AU - Shiya Huang
AU - Yeming Fu
AU - Zihao Zhou
AU - Xiaowen Sun
AU - Huadong Liu
AU - Yuhong Lai
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208998
UR - https://www.mdpi.com/1422-0067/27/20/8998
AB - 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.
SN - 1422-0067
ER -