Successful treatment of photo-damaged skin of nano-scale atRA particles using a novel transdermal delivery.
We show a novel drug delivery system (DDS) for improved all-trans retinoic acid (atRA) therapy for external treatments of photo-damaged skin. We prepared inorganic-coated atRA nanoparticles, in turn an egg-like structure in nano-scale (Nano-atRA), using boundary-organized reaction droplets. The interfacial properties of organic architectures, in atRA micelles, were used to template the nucleation of inorganic minerals. As a result, irritation and inflammation associated with atRA therapy were substantially reduced due to the complete encapsulation of the carboxylic function. Both irritative symptoms and physicochemical instability of the atRA micelle were improved. Since Nano-atRA which is prepared following to this new DDS system developmentally improved the permeability to the stratum corneum, the remarkable pharmacological effects were resulted in comparison with atRA as such as follows: (1) thicker epidermis than classical atRA treatment and (2) the overexpression of mRNA for heparin-binding epidermal growth factor (HB-EGF) as the provocation epidermal hyperplasia. Furthermore, we found a surprising boost in production of hyaluronan (HA) among the intercellular spaces of the basal and spinous cell layers in epidermis. Nano-atRA technology for atRA therapy could not only efficiently regulate keratinocyte cell proliferation and differentiation, but also markedly produce the additional benefit. Severely injured human skin by chronic ultraviolet irradiation will completely repair due to the accelerated turnover of skin tissue, which is induced by Nano-atRA.
Yamaguchi
Yoko
Y
Institute of Medical Science, St. Marianna University, School of Medicine, School of Medicine, Japan. yyamaguc@marianna-u.ac.jp
Nagasawa
Teruaki
T
Nakamura
Natsumi
N
Takenaga
Mitsuko
M
Mizoguchi
Masako
M
Kawai
Shin-Ichi
S
Mizushima
Yutaka
Y
Igarashi
Rie
R
D000279:Administration, Cutaneous; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D000078404:Epidermal Cells; D004815:Epidermal Growth Factor / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D049329:Nanostructures; D010787:Photosensitivity Disorders / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D014212:Tretinoin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D014212:Tretinoin; D004815:Epidermal Growth Factor