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Updated: Jan 20, 2026

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Penetration enhancement effects of topically applied crosslinked hyaluronic acid
Aaron Cohen1, Raphael Legouffe2, Krystal House3
1Personal Care Department, Colgate-Palmolive Company, Piscataway, New Jersey, USA.
Objective:
In this manuscript, we report that crosslinked hyaluronic acid (HA), a skincare active with well-documented hydration and skin protection benefits, can act as a penetration enhancer for the topical delivery of skincare actives. High-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) studies revealed that crosslinked HA can boost the topical delivery of both small-molecule actives and macromolecules alike.
Methods:
Porcine ear skin and human skin explants were used for the HPLC and MALDI-MSI studies, respectively. Topical delivery studies were conducted with simple cosmetic vehicles containing either the active of interest or the active of interest plus crosslinked HA. Delivery studies were conducted for 24 h, after which skin explants were analysed to measure the level of topically delivered active.
Results:
HPLC analysis revealed that crosslinked HA selectively boosted the topical delivery of hydrophilic actives, which we attributed to the strong water-binding properties of crosslinked HA. MALDI-MSI revealed that crosslinked HA could also boost the topical delivery of a medium-molecular-weight HA species (~200-400 kDa), demonstrating that the penetrating enhancing properties of crosslinked HA benefit both small molecules and macromolecules alike.
Conclusions:
Crosslinked HA can boost the topical delivery of relevant skincare actives that range in size from small-molecule actives (<500 Da) to large macromolecules (>10 000 Da) like linear HA itself. Combined with its well-established and previously documented skin benefits, this makes crosslinked HA a highly versatile ingredient for topical skincare products.
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