Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery

Gerile Candan, Hiroyuki Michiue, Sanae Ishikawa, Atsushi Fujimura, Keiichiro Hayashi, Atsuhito Uneda, Akiko Mori, Iori Ohmori, Tei-ichi Nishiki, Hideki Matsui, Kazuhito Tomizawa

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Topical therapy is the most favored form of treatment for whitening against hyperpigmentation and sunburn because it lends itself to self-administration, patient compliance, and absence of systemic adverse effects. However, transdermal delivery of hydrophilic chemicals is difficult. The main purpose of this study is to develop a delivering system of hydrophilic drugs and proteins across the skin. Hydroquinone (HQ), a well-known tyrosinase inhibitor and antimelanogenesis compound, and enhanced green fluorescent protein (EGFP) were fused with eleven poly-arginine (11R). Both HQ-11R and EGFP-11R were efficiently delivered in B16 cells, a mouse melanoma cell line. HQ-11R was as effective as HQ alone at inhibiting melanin synthesis in B16 cells. EGFP-11R was efficiently delivered into cells of the epidermis with 4-(1-pyrenyl)-butyric acid (PB), a counteranion bearing an aromatic hydrophobic moiety, in vivo, but EGFP alone or EGFP-11R without PB was not. Finally, topical application of HQ-11R with PB significantly inhibited UV irradiation-induced pigmentation in guinea pigs compared with HQ alone. These results suggest that topical therapy using poly-arginine in combination with PB is useful for the delivery of hydrophilic drugs and proteins by the transdermal route.

Original languageEnglish
Pages (from-to)6468-6475
Number of pages8
JournalBiomaterials
Volume33
Issue number27
DOIs
Publication statusPublished - Sep 2012

Fingerprint

Arginine
Butyric acid
Anions
Negative ions
Proteins
Bearings (structural)
Sunburn
Hyperpigmentation
Self Administration
Melanin
Monophenol Monooxygenase
Melanins
Pigmentation
Patient Compliance
Epidermis
Pharmaceutical Preparations
hydroquinone
1-pyrenebutyrate
Melanoma
Skin

Keywords

  • Hydroquinone
  • Poly-arginine
  • Protein transduction
  • Tat
  • Transdermal delivery
  • Tyrosinase inhibitor

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery. / Candan, Gerile; Michiue, Hiroyuki; Ishikawa, Sanae; Fujimura, Atsushi; Hayashi, Keiichiro; Uneda, Atsuhito; Mori, Akiko; Ohmori, Iori; Nishiki, Tei-ichi; Matsui, Hideki; Tomizawa, Kazuhito.

In: Biomaterials, Vol. 33, No. 27, 09.2012, p. 6468-6475.

Research output: Contribution to journalArticle

Candan, Gerile ; Michiue, Hiroyuki ; Ishikawa, Sanae ; Fujimura, Atsushi ; Hayashi, Keiichiro ; Uneda, Atsuhito ; Mori, Akiko ; Ohmori, Iori ; Nishiki, Tei-ichi ; Matsui, Hideki ; Tomizawa, Kazuhito. / Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery. In: Biomaterials. 2012 ; Vol. 33, No. 27. pp. 6468-6475.
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