title: Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery.
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.
authors: Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-Ku, Okayama, Japan.
authors: Gerile
authors: G
authors: Candan
authors: Hiroyuki
authors: H
authors: Michiue
authors: Sanae
authors: S
authors: Ishikawa
authors: Atsushi
authors: A
authors: Fujimura
authors: Keiichiro
authors: K
authors: Hayashi
authors: Atsuhito
authors: A
authors: Uneda
authors: Akiko
authors: A
authors: Mori
authors: Iori
authors: I
authors: Ohmori
authors: Tei-ichi
authors: T
authors: Nishiki
authors: Hideki
authors: H
authors: Matsui
authors: Kazuhito
authors: K
authors: Tomizawa
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000838:Anions; D020148:Butyric Acid / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016503:Drug Delivery Systems / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D057927:Hydrophobic and Hydrophilic Interactions; D006873:Hydroquinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008543:Melanins / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry*; D012880:Skin Pigmentation / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000838:Anions; D006873:Hydroquinones; D008543:Melanins; D010455:Peptides; D011721:Pyrenes; C485184:enhanced green fluorescent protein; D020148:Butyric Acid; D049452:Green Fluorescent Proteins; C015462:polyarginine; C002218:1-pyrenebutyrate; C031927:hydroquinone