Pharmaceutical Research

, Volume 22, Issue 5, pp 750–757

Comparative Study of the Skin Penetration of Protein Transduction Domains and a Conjugated Peptide

  • Luciana B. Lopes
  • Colleen M. Brophy
  • Elizabeth Furnish
  • Charles R. Flynn
  • Olivia Sparks
  • Padmini Komalavilas
  • Lokesh Joshi
  • Alyssa Panitch
  • M. Vitoria L. B. Bentley
Research Paper

DOI: 10.1007/s11095-005-2591-x

Cite this article as:
Lopes, L., Brophy, C., Furnish, E. et al. Pharm Res (2005) 22: 750. doi:10.1007/s11095-005-2591-x

Abstract

Purpose.

We examined the ability of a protein transduction domain (PTD), YARA, to penetrate in the skin and carry a conjugated peptide, P20. The results with YARA were compared to those of a well-known PTD (TAT) and a control, nontransducing peptide (YKAc). The combined action of PTDs and lipid penetration enhancers was also tested.

Methods.

YARA, TAT, YKAc, P20, YARA-P20, and TAT-P20 were synthesized by Fmoc chemistry. Porcine ear skin mounted in a Franz diffusion cell was used to assess the topical and transdermal delivery of fluorescently tagged peptides in the presence or absence of lipid penetration enhancers (monoolein or oleic acid). The peptide concentrations in the skin (topical delivery) and receptor phase (transdermal delivery) were assessed by spectrofluorimetry. Fluorescence microscopy was used to visualize the peptides in different skin layers.

Results.

YARA and TAT, but not YKAc, penetrated abundantly in the skin and permeated modestly across this tissue. Monoolein and oleic acid did not enhance the topical and transdermal delivery of TAT or YARA but increased the topical delivery of YKAc. Importantly, YARA and TAT carried a conjugated peptide, P20, into the skin, but the transdermal delivery was very small. Fluorescence microscopy confirmed that free and conjugated PTDs reached viable layers of the skin.

Conclusions.

YARA and TAT penetrate in the porcine ear skin in vitro and carry a conjugated model peptide, P20, with them. Thus, the use of PTDs can be a useful strategy to increase topical delivery of peptides for treatment of cutaneous diseases.

Key Words:

P20peptidesskintopical deliveryTATYARA

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Luciana B. Lopes
    • 1
    • 3
  • Colleen M. Brophy
    • 1
    • 2
  • Elizabeth Furnish
    • 1
  • Charles R. Flynn
    • 1
  • Olivia Sparks
    • 1
  • Padmini Komalavilas
    • 1
    • 2
  • Lokesh Joshi
    • 1
  • Alyssa Panitch
    • 1
  • M. Vitoria L. B. Bentley
    • 3
  1. 1.Biodesign InstituteArizona State UniversityTempeUSA
  2. 2.Carl T. Hayden Veterans Affairs Medical Center, PhoenixPhoenixUSA
  3. 3.Pharmacy School of Ribeirâo PretoUniversity of Sâo PauloRibeirâo Preto, SPBrazil