Abstract
The transdermal drug delivery system has been extensively
explored as a noninvasive route for drug administration.
However, the advancement of this attractive route is hindered
primarily due to complex application methods that often
require specialized equipment. To examine recombinant synthetic chromatin as a transdermal delivery vehicle for
enhanced skin penetration and cellular uptake, a modified
histone H2A protein fused with a cell-penetrating peptide
(CPP) was produced and incorporated into a 10 nm nucleosomal array using other core histones and plasmid DNA. The
cellular uptake and nuclear localization of the synthetic
chromatin were assessed using fluorescence microscopy and
flow cytometry in HeLa cells. Results demonstrated that CPPdisplayed chromatin exhibited superior cell penetration and
nuclear localization compared to control histones and chromatin. A porcine skin-based Franz cell system was utilized to
evaluate transdermal penetration. It showed significantly
enhanced passive skin penetration of CPP-displayed chromatin
compared to control groups. This study presents a novel
approach for improving the transdermal delivery of nucleic
acids and associated proteins using a modified nucleosomal
array as a delivery vehicle. The enhanced skin penetration
capabilities of the CPP-chromatin offer promising potential for
developing non-invasive gene therapy applications and transdermal delivery of therapeutic proteins or peptides.
explored as a noninvasive route for drug administration.
However, the advancement of this attractive route is hindered
primarily due to complex application methods that often
require specialized equipment. To examine recombinant synthetic chromatin as a transdermal delivery vehicle for
enhanced skin penetration and cellular uptake, a modified
histone H2A protein fused with a cell-penetrating peptide
(CPP) was produced and incorporated into a 10 nm nucleosomal array using other core histones and plasmid DNA. The
cellular uptake and nuclear localization of the synthetic
chromatin were assessed using fluorescence microscopy and
flow cytometry in HeLa cells. Results demonstrated that CPPdisplayed chromatin exhibited superior cell penetration and
nuclear localization compared to control histones and chromatin. A porcine skin-based Franz cell system was utilized to
evaluate transdermal penetration. It showed significantly
enhanced passive skin penetration of CPP-displayed chromatin
compared to control groups. This study presents a novel
approach for improving the transdermal delivery of nucleic
acids and associated proteins using a modified nucleosomal
array as a delivery vehicle. The enhanced skin penetration
capabilities of the CPP-chromatin offer promising potential for
developing non-invasive gene therapy applications and transdermal delivery of therapeutic proteins or peptides.
| Original language | English |
|---|---|
| Title of host publication | DiscoverBMB Abstracts Proceedings |
| DOIs | |
| Publication status | Published - 2025 |