Clinical and histologic findings after use of a novel combined retinol, tripeptide, and glaucine containing cream in the treatment of photo‐aged skin

Neck skin is thinner and has a more delicate dermal layer than facial skin. The studied product was specifically formulated for the neck combining a hydrating delivery system with a trifunctional corrective technology composed of 0.2% pure retinol, 2.5% tripeptide concentrate, and 5.0% glaucine complex to help improvement in signs of aging.


| INTRODUC TI ON
With fewer lipids than skin on the face, the neck's skin barrier can weaken as early as age 30.Photodamage in such areas is best treated with products that focus on the unique qualities of such delicate skin.A number of cosmeceuticals with natural or synthetic active ingredients are available in the market to treat photoaging, however, evidence based data is lacking for most.Randomized placebo controlled studies with positive outcome are available for retinoids, α-hydroxy acids such as glycolic, and some peptide etc. 1 Retinoids have strongest evidence showing clinical and histologic improvement in photoaged skin, however irritant dermatitis with retinoid therapy has limited their acceptance by patients. 2Addition of peptides and glaucine has shown to augment antiaging effect without adverse effects on skin barrier or excess transepidermal water loss. 3,4In order to minimize retinoid side effects, we combined the retinol with peptides and glaucine complex and delivered it through a novel encapsulated controlled delivery system.

| ME THODOLOGY
This study looked at the use a trifunctional corrective technology composed of 0.2% pure retinol, 2.5% tripeptide concentrate, and 5.0% glaucine complex (Tripeptide-R Neck Repair, Skinceuticals) for the cosmetic improvement of photoaged skin.The study evaluated a total of 20 healthy male or female subjects, 18 years and older, who were willing to discontinue other cosmetic products and treatments like tanning, antioxidants creams etc. and were also willing to undergo skin biopsy at baseline and at 3 months follow up.Patients with skin cancer, unstable dermatologic and medical conditions, drug allergies, pregnant or on any topical prescription medications were excluded from the study.The patients were assessed for improvements in photoaged skin using the Griffiths' Photonumeric Photoaging scale, clinical photography, and subject questionnaires (Table 1) about overall skin texture and quality.Their skin was also assessed for histologic changes in Type I collagen, Type III collagen and GAGS at baseline and post treatment using Type I and Type III collagen immunostains and Alcian blue pH 2.5 special stains respectively.
All subjects used the study cream on the face and neck for a period of 90 days.Each subject underwent a 3 mm punch biopsy of the right infra-auricular area at the start of the study and at the 3 month follow-up visit.Each subject also underwent clinical multiple-angle standardized photographs at baseline, 1 month follow up and 3 month follow up visit.
(Inclusion or exclusion criteria)
At the 1 month visit, an average 12 percent improvement was noted in the Griffiths' Photonumeric Photoaging scale.At the 3 month follow up visit this had further improved.Paired T test statistical analysis between baseline and 3 month scores, demonstrated a statistically significant p value of 0.049.(Table 3).Biopsies taken at baseline and 3 months after treatment showed comparative increase in Type I and III collagen and GAGs immunostaining at 3 month biopsies.(Figures 1, 2, 3).

TA B L E 1
Questionnaire used by subjects and investigator for assessment over the 3 month period.Consistent with evaluator noted improvement (Figure 4), subjects reported improvement in overall skin appearance, texture with reduced wrinkling at follow up visits.No adverse events were noted.

| DISCUSS ION
Photoaging is caused by photodamage and leads to premature aging of skin. 2 It depends on multiple factors such as cumulative ultraviolet exposure, sun burns, skin type, lifestyle factors etc 5 and can be assessed with prematue wrinkling, pigmentary changes, textural changes, telangiectasias, and actinic purpura on the skin etc. 6,7 When compared to facial skin, neck skin is often a more prominent indicator of aging, with often showing greater comparative loss of subcutaneous fat, dermal collagen, and elastin. 8tinoids have been widely used for treatment of acne and photoaging.Their efficacy in the treatment of photoaging, was first demonstrated by Klingman and colleagues in early 1980s. 9Retinoids influence cellular processes such as cellular growth and differentiation, cell surface alterations, and immune modulation.Retinoids are available in different forms including retinols, retinaldehyde, and retinoic acid. 10Retinol is considered 20 times less potent than tretinoin (potent prescription strength retinoid) and it requires in vivo conversion to retinoic acid to demonstrate its action. 11Duell et al demonstrated that retinol is as effective as retinoic acid in producing histologic and clinical improvement in skin. 12Retinol produces considerably less transepidermal water loss, erythema and scaling compared to retinoic on skin barrier and reduced transepidermal water loss. 13Glaucine is an alkaloid derived from yellow poppy seed which has been noted to have skin conditioning properties. 4Peptides are short amino acid sequences and demonstrate diverse range of biological properties. 14 a study by Robinson et al, topical peptides application was well tolerated by the photoaged facial skin and provided significant improvement compared to placebo in wrinkles reduction as they calculated by both quantitative technical and expert grader image analysis. 3 used a novel topical cream combination of a hydrating retinol (in an encapsulated form with timed release), in combination with tripeptide, and glaucine that was specifically formulated for the neck skin.This combination was designed for a better and efficient delivery of retinol to skin, with minimal irritation.Clinical and statistically significant improvement in signs of photoaging was noted by provider and patient as noted depicted in respective questionnaires.
These findings were also supported with histologic improvement in dermal collagen I & III and GAGs as noted by respective immunostaining of pre and post treatment skin biopsies in all subjects.
The study was limited by lack of heterogeneity with few skin of color and male participants however, it supports that combination retinol, tripeptide, and glaucine containing product can lead to clinically identifiable improvement in signs of photoaging on face and neck by increased amounts of new collagen and GAGs.

F I G U R E 1 F I G U R E 2 F I G U R E 3
Comparison of glycosaminoglycans (GAG) staining before and 3 months after treatment.Comparison of Type 3 collagen staining before and 3 months after treatment.Comparison of Type 1 collagen staining before and 3 months after treatment.acid(tretinoin), 10 which encourages more consistent usage of retinols compared to retinoic acid.Multiple studies have demonstrated that addition of peptides to antioxidants and retinoids can augment reduction of fine lines and wrinkles alongside minimizing adverse effects Patient demographics in the study.
TA B L E 3Paired T test used to compare values of Griffiths' photonumeric photoaging scale at baseline and 3 months, demonstrated statistically significant p value of 0.049.