Homoharringtonine is a transdermal granular permeation enhancer

Biochem Biophys Res Commun. 2022 Aug 6:616:140-144. doi: 10.1016/j.bbrc.2022.04.067. Epub 2022 Apr 18.

Abstract

Although modulation of claudin-1-based tight junction (TJ) in stratum granulosum is an option for transdermal absorption of drugs, granular permeation enhancers have never been developed. We previously found that homoharringtonine (HHT), a natural alkanoid, weakened intestinal epithelial barrier with changing expression and cellular localization of TJ components such as claudin-1 and claudin-4. In the present study, we investigated whether HHT is an epidermal granular permeation enhancer. Treatment of normal human epidermal keratinocytes (NHEK) cells with HHT decreased claudin-1 and claudin-4 but not zonula occludens-1 and E-cadherin. HHT lowered TJ-integrity in NHEK cells, accompanied by permeation-enhancement of dextran (4 kDa) in a dose-dependent manner. Transdermal treatment of mice with HHT weakened epidermal barrier. HHT treatment enhanced transdermal absorption of dextran with a molecular mass of up to 10 kDa. Together, HHT may be a transdermal absorption enhancer.

Keywords: Permeation enhancer; Stratum granulosum; Tight junction; Transdermal absorption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Claudin-1 / metabolism
  • Claudin-4 / metabolism
  • Dextrans* / metabolism
  • Homoharringtonine* / pharmacology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Mice
  • Tight Junctions* / metabolism

Substances

  • Claudin-1
  • Claudin-4
  • Dextrans
  • Homoharringtonine