title: Tretinoin cyclodextrin complex (RA/CyD) causes less irritation with an equal antiwrinkle effect compared with conventional tretinoin: clinical and histologic studies of photoaged skin.
abstract: BACKGROUND
  Topical tretinoin [all-trans-retinoic acid (RA)] currently is widely used to treat photoaged skin. However, undesirable side effects such as erythema, irritation, and scaling are unavoidable and limit the use of tretinoin. To address these issues, the authors developed the tretinoin cyclodextrin complex (RA/CyD), which is tretinoin encapsulated by cyclodextrin. Cyclodextrins are cyclic oligosaccharides commonly used in food additives and fabric fresheners. This study aimed to evaluate the antiwrinkle effect of RA/CyD and alleviation of the side effects compared with RA treatment alone.
  
  
  METHODS
  In this study, 12 photoaged patients completed an 8 week study using RA and RA/CyD in a double-blind manner. Before and after the treatment, the patients' evaluations, wrinkle scores, skin elasticity, and wrinkle area measurement using skin replica were evaluated. Three men were recruited for histologic analysis.
  
  
  RESULTS
  The patients reported that undesirable irritant reactions were more moderate with RA/CyD than with RA. In the assessment of wrinkle scores, skin elasticity, and wrinkle area measurement, RA/CyD demonstrated an antiwrinkle effect statistically equal to that of RA. In histology, both RA/CyD and RA demonstrated epidermal hyperplasia. In immunohistochemistry, inflammation induced by RA/CyD was more moderate than that induced by RA.
  
  
  CONCLUSIONS
  The findings show that RA and RA/CyD result in the equivalent clinical improvement for patients with photoaging. The use of RA/CyD overcomes the drawbacks of RA while possessing equal effect. It is expected that CyD will broaden tretinoin treatment.
  
  
  METHODS
  This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.
authors.affiliation: Department of Cosmetic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan. miura@psurg.med.osaka-u.ac.jp
authors.forename: Tomoe
authors.initials: T
authors.lastname: Miura
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ooe
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000279:Administration, Cutaneous; D000287:Administration, Topical; D000368:Aged; D017453:Dermatitis, Irritant / Q000517:prevention & control; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D012720:Severity of Illness Index; D012867:Skin / Q000187:drug effects; D015595:Skin Aging / Q000187:drug effects*; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage* / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D003879:Dermatologic Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D014212:Tretinoin