MDI 301, A non‐irritating retinoid, improves abrasion wound healing in both aged and diabetic skin

Abstract

MDI 301 is a picolinic acid‐substituted ester of retinoic acid (RA) and has been shown to increase epidermal thickness and pro‐collagen synthesis in organ‐cultured human skin. Unlike RA, MDI 301 does not induce expression of pro‐inflammatory cytokines or induce expression of leukocyte adhesion molecules. In the present study topical MDI 301 improves the structure and function of skin in two models of skin damage in rodents and improves dermal wound healing in these models. MDI 301 was applied daily to the skin of diabetic rats (eight weeks post treatment with streptozotocin) and to the skin of aged (14–16 month old) rats. In both 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 three days. At the end of the incubation period, culture fluids were assessed for soluble type I collagen. In both models, the level of type I collagen was increased by MDI 301, while the levels of skin irritation was virtually nonexistent. These findings demonstrate that a MDI‐301 has the beneficial effects of increasing skin healing without the traditional ill effects of skin irritation and offers a potential substitute for the parent Retinoic Acid. Work supported by NIH RO1 HL07097