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Recent evidence suggests that PEGylation is generally employed to increase molecular weight and protect the payloads and/or drug nanoparticles from proteolytic degradation (Harris and Chess, 2003), thereby expanding their applicability in Alzheimer's and enabling specific designs that (i) prolong circulation timeas PEG chain can mitigate a rapid uptake by the RES (Kong et al., 2020), (ii) play a role in physical stabilityby reducing particle agglomeration and/or protein corona effect (Guerrini et al., 2018) or providing a steric stability with targeted A aggregates (Singh et al., 2022), (iii) improve BBB penetration (Kochman et al., 2026), and (v) enable controlled drug release and improved pharmacokinetics (Turjeman et al., 2015)

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Ten days oral treatment of CIA mice with the zonulin antagonist larazotide shortly before the onset of arthritis prevented the observed increase in intestinal barrier permeability for FITC-Dextran (FD4) and attenuated arthritis symptoms (Fig