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bioRxiv · 10.1101/2025.09.11.675732

Enhanced cellular and transdermal delivery of the modified chromatin using gH625 cell-penetrating peptide

Zhang, X.·Liang, Y.·Zonta, F.·Park, J. H.
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Abstract

The transdermal drug delivery system has been used as a noninvasive route for drug administration, but often requires specialized equipment or invasive treatment. To examine recombinant synthetic chromatin as a non-invasive transdermal delivery vehicle, a modified histone H2A fused with a cell-penetrating peptide (gH625) was examined for its utility. Both in vitro porcine skin-based test and in vivo mice studies showed significantly enhanced passive skin penetration of gH625-modified chromatin compared to control groups. The gH625-H2A chromatin was examined as a delivery vehicle of EGF by displaying it at the carboxy terminus of histone H2B to enhance stability and skin penetration. The experimental results showed that the biological activities of EGF-displayed chromatin are comparable to those of the isolated EGF peptide in the HaCa-T cell line. The enhanced skin penetration capabilities of the gH625-H2A-modified chromatin offer great potential for developing non-invasive transdermal delivery of therapeutic proteins or peptides.

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Zhang, X., Liang, Y., Zonta, F., Park, J. H.. 2025-09-13. Enhanced cellular and transdermal delivery of the modified chromatin using gH625 cell-penetrating peptide. https://doi.org/10.1101/2025.09.11.675732

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