Multifaceted amelioration of cutaneous photoageing by (0.3%) retinol

Abstract

Background: Although retinol skin care products improve the appearance of photoaged skin, there is a need for an effective retinol concentration that provides skin benefits without irritation.

Objective: To compare the efficacy of topical 0.1%, 0.3% and 1% retinol in remodelling the cutaneous architecture in an in vivo experimental patch test study, and to determine tolerance of the most effective formulations when used in a daily in-use escalation study.

Methods: For the patch test study, retinol products were applied under occlusion, to the extensor forearm of photoaged volunteers (n = 5; age range 66-84 years), and 3 mm skin biopsies obtained after 12 days. Effects of different retinol concentrations, and a vehicle control, on key epidermal and dermal biomarkers of cellular proliferation and dermal remodelling were compared to untreated baseline. Separately, participants (n = 218) recorded their tolerance to 0.3% or 1% retinol over a six-week, approved regimen, which gradually increased the facial applications to once nightly.

Results: Retinol treatment induced a stepwise increase in epidermal thickness and induced the expression of stratum corneum proteins, filaggrin and KPRP. 0.3% retinol and 1% retinol were comparably effective at inducing keratinocyte proliferation in the epidermis, whilst reducing e-cadherin expression. Fibrillin-rich microfibril deposition was increased following treatment with 0.3% and 1% retinol (p < 0.01); other dermal components remained unaltered (e.g., fibronectin, collagen fibrils, elastin), and no evidence of local inflammation was detected. The in-use study found that 0.3% retinol was better tolerated than 1% retinol, with fewer and milder adverse events reported (χ² (1) = 23.97; p < 0.001).

Conclusions: This study suggests that 1% and 0.3% retinol concentrations were similarly effective at remodelling photodamaged skin in an in vivo model of long-term use. Use of 0.3% retinol in the escalation study was associated with fewer adverse reactions when applied daily. Hence, 0.3% retinol may be better tolerated than 1% retinol, thereby allowing longer-term topical application.

Keywords: formulation; photodamage; skin barrier; skin physiology/structure.

FIGURE 1

Retinol treatment induces keratinocyte proliferation and expression of proteins required for skin barrier function. (a) Representative images showing immunostaining for keratinocyte proline‐rich protein [KPRP], filaggrin and e‐cadherin/Ki67 staining within the epidermis. (b) Quantification of epidermal thickness, (c) filaggrin abundance, (d) melanin distribution and (e) Ki67 expression are shown. Statistical significance for differences between treatments compared with the baseline control was assessed by repeated‐measures one‐way ANOVA followed by a Dunnett's multiple comparison test (*p < 0.05, **p < 0.01).

FIGURE 2

Retinol (0.3%) induces significant deposition of fibrillin‐rich microfibril within the papillary dermis. (a) Representative images showing immunostaining for fibrillin‐rich microfibrils at the papillary dermis. (b) Quantification of fibrillin‐rich microfibril deposition data, presented as the mean ± SEM. Statistical significance for differences between the treatments compared to the baseline control was assessed by repeated‐measures one‐way ANOVA followed by a Dunnett's multiple comparison test (*p < 0.05).

FIGURE 3

Superior tolerance of 0.3% and 1% retinol by consumers using a daily un‐use regimen. Consumer self‐reported tolerance profiles of individuals applying 0.3% (n = 115) and 1% (n = 103) retinol formulations to the face in a six‐week regimen. Data shows the percentage of individuals reporting their reactions to the formulations as mild, moderate or severe. Participants reporting no reactions were considered fully tolerant to the retinol formulations. These individuals were categorized with those reporting mild reactions that were considered to fall within the scope of acceptable responses to a topical retinol skin care regimen.