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Rayman MP, Stranges S, Griffin BA, Pastor-Barriuso R, Guallar E

cleavage sites pH-dependent stability profiles (pH 1.5-8.0) Temperature stability assessment Oxidative and hydrolytic degradation pathways Stabilization Technology Research: Protease inhibitor effectiveness in protecting oral peptides Mucoadhesive polymer effects on gastric residence time Cyclodextrin complexation for stability enhancement PEGylation and chemical modification effects on oral bioavailability Laboratory Handling and Administration Protocols Capsule Storage: Store at room temperature (15-30C) in sealed container Protect from moisture using desiccant packets Keep away from direct light exposure Stable for extended periods at room temperature (exceptional for peptides) No refrigeration required (unlike most peptide formulations) Oral Administration in Research Models: Rodent Models: Oral gavage administration using appropriate gavage needles Capsule can be opened and contents suspended in water or vehicle Typical volumes: 0.2-0.5 mL per mouse, 1-2 mL per rat Fed vs

*Correspondence: Kamil Kua, [email protected];[email protected] Jaevi, [email protected] ORCID: Jelena Dumanovi, orcid.org/0000-0002-8078-9878 Eugenie Nepovimova, orcid.org/0000-0003-0281-246X Maja Nati, orcid.org/0000-0002-6610-297X Kamil Kua, orcid.org/0000-0001-9664-1109 Vesna Jaevi, orcid.org/0000-0001-5137-2638 These authors have contributed equally to this work This article was submitted to Plant Cell Biology, a section of the journal Frontiers in Plant Science Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers

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Direct antioxidant administration, such as vitamins C and E, has also shown limited efficacy due to poor bioavailability and inadequate targeting of mitochondrial ROS production 17