Homoharringtonine is a transdermal granular permeation enhancer

Transdermal drug delivery remains limited by the stratum granulosum's barrier function. While claudin-1-based tight junctions are known to regulate permeability, no granular enhancers have been developed. Prior research has shown that claudin-1 and claudin-4 influence epithelial permeability. Claudin-4's role in skin permeability is less understood compared to claudin-1. Claudin-1 is a key component of tight junctions in keratinocytes. Claudin-1 disruption increases paracellular permeability. Claudin-1 expression is sensitive to external agents. Claudin-1 modulation has been tested in intestinal models.

This work aimed to evaluate homoharringtonine's effect on epidermal permeability. The study focused on whether HHT could alter tight junctions in keratinocytes. Researchers sought to test HHT's ability to enhance drug absorption through the skin. The goal was to determine if HHT could act as a granular permeation enhancer. The study's focus was on stratum granulosum permeability. The motivation was to expand transdermal delivery options. The investigation centered on claudin-1 and claudin-4 expression. The study tested HHT's impact on dextran permeation.

The study used normal human epidermal keratinocytes (NHEK) for experiments. Claudin-1 and claudin-4 expression was analyzed via Western blot. Tight junction integrity was assessed using permeability assays. Dextran permeation was measured at 4 kDa and 10 kDa. Mice were used to test transdermal absorption in vivo. HHT treatment effects were evaluated in a dose-dependent manner. Epidermal barrier function was measured after HHT application. The study compared HHT-treated and control groups.

HHT reduced claudin-1 and claudin-4 in NHEK cells. Claudin-1 levels decreased significantly with HHT treatment. Claudin-4 expression was also lowered by HHT exposure. Zonula occludens-1 and E-cadherin remained unchanged. Dextran permeation increased in a dose-dependent fashion. Transdermal dextran absorption reached up to 10 kDa. Mice treated with HHT showed weakened epidermal barriers. HHT enhanced permeability without affecting other junction proteins.

HHT may function as a transdermal permeation enhancer. The compound appears to target claudin-1 and claudin-4. HHT's effect is specific to granular layer tight junctions. The study suggests HHT could improve drug absorption through the skin. Dextran permeation increased with HHT treatment. Claudin-1 and claudin-4 are likely key mediators of this effect. The findings support HHT's potential as a permeation enhancer. The results are consistent with prior intestinal barrier studies.