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Inflammation-associated changes such as altered epithelial permeability, mucosal ulceration, bleeding, and edema, together with marked heterogeneity in histopathological featuresincluding mucus thickness, enzymatic activity, oxidative stress levels, and microbiota compositioncomplicate the predictable behavior of NPs across different disease stages and phenotypes ( 3.3 Off-Target effects and limited targeting specificity Many NP-based delivery systems rely on passive targeting mechanisms analogous, which are highly variable in the inflamed gut and lack spatial precision (Lin et al., 2025)

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