Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams

Griffiths, C.E.M.

doi:10.1001/archderm.131.9.1037

Cited by 68 publications

(81 citation statements)

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“…[18][19][20][21][22][23][24][25] Although retinoids have beneficial activities, skin irritation is commonly seen following topical application of RA. [26][27][28] If skin irritation is too severe, retinoid use will simply be discontinued by most users. Equally important, excessive irritation may negate beneficial effects that would otherwise be seen, or actually increase sensitivity to wound formation.…”

Section: Discussionmentioning

confidence: 99%

“…Although it is generally believed that improved wound healing in retinoid-treated skin reflects these dermal activities, it is important to keep in mind that retinoids are broad-acting molecules that influence the functioning of other elements in the skin, as well. Retinoid treatment increases keratinocyte proliferation and motility, 26,27,39 properties essential for rapid wound closure. Given the regenerative effects of retinoid use on both the dermal and epidermal component of the skin, it is not surprising that retinoids should be considered for use as wound-preventative or woundhealing agents.…”

Section: Discussionmentioning

confidence: 99%

“…26 Irritated skin is characterized by redness, dryness, and flaking at the treated site. At the histological level, one sees a perivascular accumulation of mononuclear cells, with neutrophils and monocytes scattered throughout the dermis and occasional micro-abscesses in the dermis or epidermis.…”

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MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin

Warner

Bhagavathula

Nerusu

et al. 2008

Wound Repair Regeneration

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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.Minor abrasions that occur in healthy skin are expected to heal without incident. Interventions are designed primarily to prevent infection and to provide support for the body's own regenerative mechanisms. In contrast, wounds in chronically damaged and atrophic skin often go on to form nonhealing ulcers with devastating consequences. Diabetes alone is a contributing factor in up to 70% of the > 55,000 amputations that occur annually. [1][2][3][4] Skin that has become atrophic as a consequence of the aging process also demonstrates impaired wound healing, 5-7 as does skin that has been damaged as a result of extended corticosteroid use. [8][9][10] The majority of wound-healing research is directed toward understanding the pathophysiology of impaired wound healing and identifying interventions that can mitigate the critical patho-physiological events.Several past studies have demonstrated the efficacy of all-trans retinoic acid (RA) and its parent compound all-trans retinol (ROL, vitamin A) in wound healing. Although most studies have focused on wounds in the skin, [11][12][13][14][15][16][17] retinoid efficacy has also been demonstrated in healing of wounds in other tissues (bone, cornea, respiratory tract, upper digestive system, and gut). 27 Likewise, skin irritation is also a complication with synthetic retinoidal agents currently on the market. 28 Irritation is a major cause of non-compliance among retinoid users. In addition, excessive irritation may counteract the beneficial effects of retinoid use or actually predispo...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin

Warner

Bhagavathula

Nerusu

et al. 2008

Wound Repair Regeneration

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“…Others have shown that vitamin A mediates events similar to RA but is less irritating in human skin [15]. It has also been shown that by carefully controlling the dosage, irritation can be mitigated under conditions in which beneficial activities remain [12]. In a past study we showed that a synthetic, estersubstituted retinoid (i.e., MDI 301) was similar to RA in its ability to induce epidermal hyperplasia in hairless mice and to induce a thickening of the collagen band immediately beneath the epidermis [28].…”

Section: Discussionmentioning

confidence: 99%

“…Irritated skin is characterized by redness, dryness and flaking at the treated site. At the histological level, one sees a perivascular accumulation of mononuclear cells, with neutrophils and monocyes scattered throughout the dermis and occasional micro-abscesses in the dermis or epidermis [12]. Alltrans retinol (vitamin A), the parent compound of RA, tends to be less irritating than RA in most cases, but even with this agent, significant irritation is observed in many individuals [15].…”

Section: Introductionmentioning

confidence: 99%

MDI 301, a non-irritating retinoid, induces changes in human skin that underlie repair

2006

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Previous studies have demonstrated that all-trans retinoic acid (RA) increases collagen production and decreases matrix metalloproteinase (MMP) activity in organ-cultured human skin. Decreased MMP activity is associated with up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1). These changes are accompanied by a hyperplastic response in the epidermis. Here we show that a synthetic picolinic ester-substituted retinoid (designated as MDI 301) has comparable effects to those of RA in regard to these activities. What makes these findings of interest is that RA also stimulates elaboration of several pro-inflammatory cytokines and up-regulates leukocyte adhesion molecules in organ-cultured skin. MDI 301 does not induce such changes or is much less active. In a past study we showed that while RA was irritating to the skin of topically treated hairless mice, MDI 301 was essentially non-irritating under the same conditions [Varani et al. (2003) Arch. Dermatol Res 295:255-262]. Taken in conjunction with the findings from the past study, the present data suggest that MDI 301 will be similar to RA in capacity to repair damaged skin, but will be effective under conditions that are not irritating. These findings, thus, suggest that retinoid efficacy and clinically relevant irritancy are not inextricably linked. Potential for efficacy under conditions in which irritation is not observed is a strong rationale for further development of MDI 301 as a skin-repair agent.

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Improvement of Naturally Aged Skin With Vitamin A (Retinol)

Kafi¹,

Kwak²,

Schumacher³

et al. 2007

Arch Dermatol

185

115

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The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities.Intervention: Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks.Main Outcome Measures: Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas.Results: After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinoltreated and vehicle-treated skin for changes in fine wrinkling scores (−1.64 [95% CI, −2.06 to −1.22] vs −0.08 [95% CI, −0.17 to 0.01]; PϽ.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P =.02 [n=6]) and procollagen I immunostaining (P=.049 [n=4]) compared with vehicle.Conclusions: Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

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Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams

Cited by 68 publications

References 0 publications

MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin

MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin

MDI 301, a non-irritating retinoid, induces changes in human skin that underlie repair

Improvement of Naturally Aged Skin With Vitamin A (Retinol)

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