Climbazole Boosts Activity of Retinoids in Skin

Abstract

Objective

To explore if climbazole enhances retinoid-associated biological activities in vitro and in vivo.

Methods

Primary human dermal fibroblasts (HDFs) were treated from six to 48 hours with either retinoids (retinol, retinyl propionate, retinyl palmitate) alone or in combination with climbazole, then assessed for cellular retinoic acid-binding protein 2 (CRABP2) mRNA expression by RT-qPCR. Next, skin equivalent (SE) cultures were topically treated with a retinol or retinyl propionate, and with or without climbazole, then measured for biological changes in retinoid biomarkers. Lastly, an IRB-approved clinical study was conducted on the outer forearm of 16 subjects to ascertain the effects of low (0.02%) or high (0.1%) levels of retinol, retinyl propionate (0.5%), climbazole (0.5%) or a combination of retinol (0.02%) /climbazole (0.5%). Indicators of retinoid activities were measured after 3 weeks.

Results

Treatment of HDFs with retinol or retinyl propionate were unaffected by climbazole but alone, resulted in a significantly (p<0.01) higher sustained CRABP2 mRNA expression than those treated with retinyl palmitate or vehicle control. In SEs, climbazole combined with either retinol or retinyl propionate, boosted retinoid related activity greater than the retinoid only, reflected by a dose-response, down-regulation of loricrin (LOR) and induction of keratin 4 (KRT4) proteins. In vivo, retinol (0.1%) and retinyl propionate (0.5%) significantly increased most evaluated biomarkers, as expected. Low dose retinol or climbazole alone did not increase these biomarkers; however, in combination, significant (p<0.05) increases in retinoid and aging biomarkers were detected.

Conclusion

Climbazole boosted retinoid activity both in the SE model, after a combined topic treatment with either retinol or retinyl propionate, and in vivo, in combination with a low level of retinol. Based upon the evidence presented here, we suggest that the topical skin application of climbazole in combination with retinoids, could deliver skin aging benefits more than a less robust retinoid alone.

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