Premium
MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin
Author(s) -
Warner Roscoe L.,
Bhagavathula Narasimharao,
Nerusu Kamalakar,
Hanosh Andrew,
McClintock Shan D.,
Naik Madhav K.,
Johnson Kent J.,
Ginsburg Isaac,
Varani James
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2007.00338.x
Subject(s) - retinoid , retinoic acid , wound healing , human skin , matrix metalloproteinase , hyaluronic acid , abrasion (mechanical) , irritation , proinflammatory cytokine , pharmacology , medicine , chemistry , in vivo , inflammation , surgery , biochemistry , immunology , biology , anatomy , mechanical engineering , genetics , microbiology and biotechnology , engineering , gene
MDI 301 is a picolinic acid‐substituted ester of 9‐ cis retinoic acid. It has been shown in the past that MDI 301 increases epidermal thickness, decreases matrix metalloproteinase (MMP) activity, and increases procollagen synthesis in organ‐cultured human skin. Unlike all‐trans retinoic acid (RA), MDI 301 does not induce expression of proinflammatory cytokines or induce expression of leukocyte adhesion molecules in human skin. In the present study we examined topical MDI 301 treatment for ability to improve the structure and function of skin in three models of skin damage in rodents and for ability to improve abrasion wound healing in these models. MDI 301 was applied daily to the skin of rats treated with the potent corticosteroid, clobetasol propionate, to the skin of diabetic rats (8 weeks posttreatment with streptozotocin) and to the skin of aged (14–16‐month‐old) rats. In all three models, subsequently induced abrasion wounds healed more rapidly in the retinoid‐treated animals than in vehicle‐treated controls. Immediately after complete wound closure, tissue from the wound site (as well as from a control site) was put into organ culture and maintained for 3 days. At the end of the incubation period, culture fluids were assessed for soluble type I collagen and for MMPs‐2 and ‐9. In all three models, the level of type I collagen was increased and MMP levels were decreased by MDI 301. In all three models, skin irritation during the retinoid‐treatment phase was virtually nonexistent.