Deoxycholic Acid-Grafted Carboxymethyl Chitosan Nanomicelles Embedded in Alginate Microspheres for Oral Mangiferin Delivery in Experimental Colitis
5 affiliations
- 1Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, People’s Republic of China
- 2Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics, Nanning, Guangxi, People’s Republic of China
- 3Translational Medicine Research Center, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
- 4College of Food and Quality Engineering, Nanning University, Nanning, Guangxi, People’s Republic of China
- 5Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China
Abstract
Purpose: To develop a hierarchical polysaccharide formulation combining nanoscale loading of hydrophobic mangiferin (MGF) with microscale gastrointestinal protection, and to evaluate it in dextran sulfate sodium (DSS)-induced colitis.
Methods: Carboxymethyl chitosan grafted with deoxycholic acid (DA–CMCS) was self-assembled with MGF into nanomicelles (MGF/DA–CMCS SNM), which were embedded by electrospray into Ca2⁺-cross-linked alginate microspheres (MGF/DA–CMCS@SA MS). It was assessed by physicochemical characterization, sequential pH release and gastrointestinal stability, carrier fluorescence imaging, cell assays, a DSS proof-of-concept model, 16S rRNA and RNA sequencing, and short-term compatibility tests.
Results: The nanomicelles measured 120.7 ± 0.9 nm, with a PDI of 0.342 ± 0.019, a zeta potential of −24.2 ± 1.0 mV and an apparent encapsulation efficiency of 88.03% ± 0.58%; the microspheres measured 110.3 ± 2.6 µm. Alginate encapsulation suppressed release at pH 1.2 and accelerated it at intestinal pH, consistent with microspheres remaining intact in simulated gastric fluid and disintegrating in intestinal fluid. In vitro, the system scavenged radicals, lowered intracellular ROS, protected cells from oxidative injury and attenuated inflammatory macrophage activation. After oral administration, Cy5-labeled microspheres gave stronger intestinal fluorescence than nanomicelles alone; as Cy5 labeled the carrier, this reports carrier distribution, not tissue MGF concentration. In DSS colitis, it attenuated body-weight loss, DAI, colon shortening and histological damage, and was associated with epithelial barrier-marker changes and microbiota and transcriptomic shifts, with short-term in vitro and in vivo compatibility.
Conclusion: The nanomicelle-in-microsphere system provides proof-of-concept intestinal pH-responsive oral delivery for MGF. Direct pharmacokinetic measurement, carrier-only controls, morphometric histopathology, mechanistic validation, longer-term safety testing and process-scale characterization remain necessary.
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BibTeX
@article{liu2026deoxycholic,
title = {{Deoxycholic Acid-Grafted Carboxymethyl Chitosan Nanomicelles Embedded in Alginate Microspheres for Oral Mangiferin Delivery in Experimental Colitis}},
author = {Chengzhi Liu and Yueyue Li and Nan Jiang and Weiwei He and Zhiran Xu and Yanwen Zhang and Xianhua Wu and Jiaxia Jiang and Bin Zheng and Changhua Lin and Yifei Xiang and Yucheng He and Chuang Xu and Zhengmin Liang and Jiakang He},
journal = {International Journal of Nanomedicine},
year = {2026},
month = nov,
doi = {10.2147/ijn.s640625},
url = {https://doi.org/10.2147/ijn.s640625},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Deoxycholic Acid-Grafted Carboxymethyl Chitosan Nanomicelles Embedded in Alginate Microspheres for Oral Mangiferin Delivery in Experimental Colitis
AU - Chengzhi Liu
AU - Yueyue Li
AU - Nan Jiang
AU - Weiwei He
AU - Zhiran Xu
AU - Yanwen Zhang
AU - Xianhua Wu
AU - Jiaxia Jiang
AU - Bin Zheng
AU - Changhua Lin
AU - Yifei Xiang
AU - Yucheng He
AU - Chuang Xu
AU - Zhengmin Liang
AU - Jiakang He
PY - 2026
DA - 2026/11/05
JO - International Journal of Nanomedicine
DO - 10.2147/ijn.s640625
UR - https://doi.org/10.2147/ijn.s640625
AB - Purpose: To develop a hierarchical polysaccharide formulation combining nanoscale loading of hydrophobic mangiferin (MGF) with microscale gastrointestinal protection, and to evaluate it in dextran sulfate sodium (DSS)-induced colitis. Methods: Carboxymethyl chitosan grafted with deoxycholic acid (DA–CMCS) was self-assembled with MGF into nanomicelles (MGF/DA–CMCS SNM), which were embedded by electrospray into Ca2⁺-cross-linked alginate microspheres (MGF/DA–CMCS@SA MS). It was assessed by physicochemical characterization, sequential pH release and gastrointestinal stability, carrier fluorescence imaging, cell assays, a DSS proof-of-concept model, 16S rRNA and RNA sequencing, and short-term compatibility tests. Results: The nanomicelles measured 120.7 ± 0.9 nm, with a PDI of 0.342 ± 0.019, a zeta potential of −24.2 ± 1.0 mV and an apparent encapsulation efficiency of 88.03% ± 0.58%; the microspheres measured 110.3 ± 2.6 µm. Alginate encapsulation suppressed release at pH 1.2 and accelerated it at intestinal pH, consistent with microspheres remaining intact in simulated gastric fluid and disintegrating in intestinal fluid. In vitro, the system scavenged radicals, lowered intracellular ROS, protected cells from oxidative injury and attenuated inflammatory macrophage activation. After oral administration, Cy5-labeled microspheres gave stronger intestinal fluorescence than nanomicelles alone; as Cy5 labeled the carrier, this reports carrier distribution, not tissue MGF concentration. In DSS colitis, it attenuated body-weight loss, DAI, colon shortening and histological damage, and was associated with epithelial barrier-marker changes and microbiota and transcriptomic shifts, with short-term in vitro and in vivo compatibility. Conclusion: The nanomicelle-in-microsphere system provides proof-of-concept intestinal pH-responsive oral delivery for MGF. Direct pharmacokinetic measurement, carrier-only controls, morphometric histopathology, mechanistic validation, longer-term safety testing and process-scale characterization remain necessary.
SN - 1176-9114
SN - 1178-2013
ER -