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Impact of molecular weight on the permeation enhancement and barrier interaction of fucoidan as a transdermal delivery candidate

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Fucoidan (FPS), a sulfated polysaccharide isolated from brown algae with a molecular weight ranging approximately from 5 to 200 kDa, exhibits diverse bioactivities, yet its high molecular weight (HMW) restricts topical bioavailability. This study explored the molecular-weight-dependent transdermal behavior of FPS and its underlying interaction mechanisms with the skin barrier. To address this, FPS fractions (6 to 103 kDa) were prepared via controlled oxidative degradation. In vitro permeation studies combined with Confocal Laser Scanning Microscopy (CLSM) visualization revealed a critical molecular weight threshold of approximately 11 kDa. HMW-FPS were mainly retained on the skin surface, whereas low molecular weight FPS (LMW-FPS, ≤11 kDa) penetrated into the viable epidermis and dermis. ATR-FTIR spectroscopy was employed to elucidate the underlying mechanism, which revealed that LMW-FPS overcomes the skin barrier through synergistic structural modulations: (1) it enhances intercellular lipid fluidity, accompanied by a reduction in CH2 stretching vibration intensity; (2) it induces conformational changes in keratin via direct electrostatic interactions, promoting the transition from α-helices to β-sheets. Furthermore, histological evaluation confirmed that FPS treatment caused no obvious skin irritation. These findings demonstrate that LMW-FPS acts as a safe, reversible modulator of the stratum corneum (SC) barrier, providing a promising strategy for the design of polysaccharide-based transdermal delivery systems.

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Fucoidan Various molecular weights Transdermal penetration Stratum corneum barrier Cosmetic biomaterials

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