Work

Deoxycholic Acid-Grafted Carboxymethyl Chitosan Nanomicelles Embedded in Alginate Microspheres for Oral Mangiferin Delivery in Experimental Colitis

Year: 2026

Type: article

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: ⁺-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.

Source: International Journal of Nanomedicine

DOI: 10.2147/ijn.s640625