Abstract
Background
Actually, the use of chemical peels in cosmetics and dermatology continues to grow due to their versatility, clinical endpoint–directed predictability, and favorable risk profile in comparison to lasers. The chemical peel is a generally safe method for treatment of some skin disorders and to refresh and rejuvenate the skin. The major challenge of chemical peels is the tolerability, that is because of sensitive skin which is one of the most common skin disorders.
Aim
The aim of this study was to evaluate the effectiveness of the new Miamo Renewal Peel Serum formulated with a pool of new generation acids (ELPA25™) on sensitive skin with respect to mandelic acid serum only and with respect to placebo comparison.
Materials and Methods
The “in vivo” study following the half‐face experimental protocol active versus placebo involved 30 healthy Caucasian female volunteers between 25 and 64 years, with sensitive skin, who were divided into two different groups. ELPA25™ serum was applied in one group three times a week for 8 weeks. The other group, with the same protocol, applied an active serum containing mandelic acid, as control, versus placebo. In particular, skin moisturizing, skin viscoelastic properties, skin surface smoothness, wrinkle reduction, and stratum corneum renewal were evaluated.
Results
Renewal Peel Serum was very well tolerated from sensitive skin. A significant decrease in skin roughness and wrinkle breadth, and an improvement in firmness and in skin elasticity, was observed after 2 months of treatment with respect both to mandelic acid serum and to placebo comparison.
Conclusions
Scientific protocol using self‐controlled study methodology and noninvasive skin bioengineering techniques with adequate statistical methods were able to evaluate both the safety and the efficacy of the new Miamo Renewal Peel Serum. This study highlighted that the Miamo Renewal Peel Serum formulated with a patent‐pending mixture of new generation acids (ELPA25™) exerts many beneficial effects and it can be successfully employed for sensitive skin.
Keywords: chemical peeling, lactobionic acid, mandelic acid, sensitive skin
1. INTRODUCTION
Chemical peeling is a popular and generally safe method for treatment of some skin disorders and to refresh and rejuvenate the skin. 1 , 2 , 3
Despite past predictions of their disappearance in favor of lasers, the overall use of home chemical peels continues to grow. The versatility, clinical endpoint–directed predictability, and favorable risk profile of chemical peels proffered by these latest advancements affirm that this modality is essential to treat patients with wrinkles, dyschromias, acne, and melasma. The main issue of chemical peels is their skin tolerability, especially in sensitive skin.
Sensitive skin can be defined as an alteration of skin barrier function and it may occur in two forms: objective and subjective. In the subjective form, usually self‐diagnosed, the patient complains of symptoms, without visible dermatitis. Itching, burning, stinging, and a tight sensation are constantly present. Erythema, dryness, or rash are sometimes described.
Otherwise, the objective form can present clinical lesions, such as erythema, papules, and vesicles. The alteration of the protective function of the skin barrier is favored by some kind of dermatitis such as atopic dermatitis and acne. There are predisponent factors to sensitive skin such as ethnicity, gender, age, presence of other dermatoses, environmental factors. Sensitive skin has historically been self‐reported far more often in women than in men. It is believed that there exist a biological plausibility for greater sensitivity, as thickness of the epidermis was observed to be greater in men than in women and hormonal differences which may produce inflammatory sensitivity in women have also been demonstrated. 4 In the western world, about 38.2% of men and 51.4% of woman think they have sensitive skin. 5 , 6 , 7 The nasolabial are the most sensitive region of the facial area, followed by the cheekbones, chin, forehead, and upper lip. Factors that contribute to this are probably the thinner skin barrier and the greater number of nerve endings on these face areas.
The main hypothesis attributed to the occurrence of sensitive skin is the increase in the permeability of the stratum corneum, leading to greater penetration of substances and also to water loss. There is an inverse relation between corneal layer thickness and skin permeability. The decrease in the thickness of the corneal layer facilitates the penetration of substances capable of inducing the release of cytokines, leukotrienes, and prostaglandins. These mediators induce the formation of neurotransmitters which stimulate the nerve endings. Measurement of transepidermal water loss (TEWL) has been used to aid in the diagnosis of sensitive skin. Thus, adequate hydration of the skin improves the symptomatology of patients with sensitive skin.
The choice of the appropriate peeling for patients with sensitive skin must be done carefully, focusing on delicate new generation acids with large molecular weights to decrease the possibility of deep penetration as mandelic acid, gluconolactone, and lactobionic acid. 8
Among chemical substances used for peeling, mandelic acid is one of the Alpha‐Hydroxy Acid (AHA) that penetrates the skin slowly and evenly, making it an ideal peeling agent in sensitive skin. It is used to treat acne, hyperpigmentation, and aging. It is the safest agent of all of AHA, and therefore, it is safe if used in high concentrations in all skin types. 9 , 10 Mandelic acid is a natural derivative of bitter almonds and acts gently exfoliating the skin. It has the function of dissolving the bonds between the dead cells on the surface of the skin. It has large size, so it penetrates very slowly into the skin, making a softer absorption, and therefore, causing less irritation. One of mandelic acid's most advantageous chemical properties is its LogP value (0.68), it has both lipofilic and idrofilic properties; its idrofilic characteristic enables the molecule to be absorbed once it arrives to the derma (hydrophilic environment) where it can promote collagen and proteoglycans synthesis and promotes the process of skin rejuvenation.
It has antibacterial effects and can be used to reduce inflammation by acne. It can be used for sensitive and rosacea skin and melasma.
Phytic acid is an alpha‐hydroxy acid that is derived from grains, legumes, and rice. Phytic acid is one of the gentlest of all acids used for chemical peeling and causes little exfoliation of the skin, for this reason is usually used in tandem with other acids because phytic acid often boosts their effectiveness. His major activity, in fact, is to prevent the appearance of dark spots and brighten the skin. Phytic acid has this activity thanks to two main mechanisms of action the first is inhibition of melatonin synthesis by binding and seizing copper (Cu) basic cofactor for tyrosinase's activity. The second mechanism concerns the ability to inhibit the melanin oxidation. The benefits of phytic acid include skin brightening effects, improvement of the dark spots appearance in the skin and the reduction of free radical damage.
Among others peeling substances, gluconolactone can be considered one of the most recent ingredient in the market. Gluconolactone, 3,4,5‐trihydroxy‐ 6‐ (hydroxymethyl)oxan‐2‐ one (C6H10O6), is a derivative of oxidized lactone glucose, in the form of a white solid, crystalline, almost odorless with a sweet taste. It is a polyhydroxy acid (PHA) that releases gluconic acid after the hydrolytic action of the moisture present on the skin. 11 Applied to the skin, it promotes exfoliation and cell renewal, modulating the process of keratinization, breaks the intercellular bonds and then promotes the restoration of the damaged skin barrier.
Because of its structure, it combines the properties of alpha‐hydroxy acids with the specific properties of glucose, which is able to effectively reduce water diffusion and evaporation. The main difference between gluconolactone and AHAs or BHAs (beta‐hydroxy acids) is that it presents numerous hydroxyl groups which allows the molecule to work as a humectant. This means that gluconolactone acts as an exfoliating acid, but also as a moisturizer. It has moisturizing, soothing, and lightening properties, working well on dry skin.
Another main difference between PHAs and AHAs or BHAs is the chemical structure, PHAs are much larger molecules and this characteristic allows them to penetrate the skin more slowly, which is another reason it's gentler and a good option for the sensitive skin; in fact, it avoids tingling, burning, or redness.
Gluconolactone (GLA) offers great promise for sensitive skin care. Improves the protective barrier function of the stratum corneum by strengthening, sealing, and reducing the transepidermal water loss (TEWL). This latter skin parameter became very high in case of skin barrier damage. 11 It is recommended for post‐dermatological use in patients with diseases such as rosacea and dermatitis. It also has anti‐acne properties and has been seen to have positive effects on enlarged pores. For acne, a lotion with 14% gluconolactone was used and was seen to be more effective in reducing acne than 5% benzoyl peroxide, causing less irritation. 8
Lactobionic acid represents a new generation of AHA that has a polyhydroxyl structure (so‐called polyhydroxyl acid); it has been proven to provide structural and smoothing benefits to the skin, thus providing multiple anti‐aging advantages. 12
Lactobionic acid has antioxidant property that is at least partly due to metal chelation preventing skin changes related to aging. Specifically, chelation may be the main mechanism through which lactobionic acid functions as an inhibitor of MMPs (Matrix metalloproteinase). MMP enzymes are responsible for degrading the extracellular matrix of the skin to facilitate cell migration, among other beneficial effects. However, excessive MMP activity reduces the structural integrity of the extracellular matrix of the skin, causing wrinkles, skin laxity, and telangiectasias. Increased MMP activity, along with a natural age‐related decline of MMP inhibitors activity, is one of the consequences of photoaging. In particular, MMP9 is a gelatinase that attacks gelatin, elastin, and collagen type IV, V, and X as substrates. 13
When used alone, both as a preventive and active treatment, lactobionic acid provides a beneficial anti‐aging. In particular, the compound is a strong wetting, does not irritate the skin and provides smoothing and moisturizing benefits to the skin. Lactobionic acid solutions can be used in case of dry, reddened, and itchy skin. 14 , 15
Lactobionic acid has also been shown to be gentle on the skin without causing burning and irritation also associated with some AHAs.
In this work, a new patent‐pending mixture of actives (ELPA25™) are proposed as a gentle anti‐aging peeling solutions for all types of skin. 16 Miamo use ELPA25™ for Renewal Peel Serum, market leader product in the Facial Exfoliants segment (Facial Treatments) for italian pharmacies. 17
The main aim of this work was to present a scientific protocol in order to evaluate the efficacy of topical treatment based on ELPA25™ with different claimed effects. The objective of these experimental studies was to test the effects of ELPA25™ on skin moisturization, skin surface smoothness, the presence of wrinkles, skin viscoelastic properties, and cell renewal. For this purpose, a serum containing only mandelic acid was used as control.
2. MATERIALS AND METHODS
2.1. Materials
Serum A: Propylene glycol, Aqua, Mandelic acid, Hydroxyethylcellulose, Sodium hydroxide. This serum was used as reference.
Serum B: Renewal Peel Serum based on ELPA25™ hereinafter called ELPA25™ serum: Propylene glycol, Aqua, Mandelic acid, Lactobionic acid, Phytic acid, Gluconolactone, Hydroxyethylcellulose, Sodium hydroxide, Caprylyl glycol, Acetyl hexapeptide‐8.
Placebo serum: Aqua, Propylene glycol, Hydroxyethylcellulose, Hydroxyacetophenone, Caprylyl glycol, 1,2‐Hexanediol, Sodium hydroxide, Tropolone.
Commercial cleanser. Ingredients: Aqua, Glycerin, Disodium Laureth Sulfosuccinate, Potassium Olivoyl Hydrolyzed Wheat Protein, Allantoin, Rosa Centifolia Flower Oil, Chondrus Crispus Extract, Eriobotrya Japonica Leaf Extract, Xanthan Gum, Phenoxyethanol, Phenethyl Alcohol, Citric Acid, CI 16255, Propylene Glycol, Ethoxydiglycol, Caprylyl Glycol, Potassium Chloride, 1,2‐Hexanediol, Tropolone, distributed by Medspa.
Commercial base cream. Ingredients: Aqua, Simmondsia Chinensis (Jojoba) Seed Oil, Prunus Armeniaca (Apricot) Kernel Oil, Squalane, Polyacrylamide, C13‐14 Isoparaffin, Sodium Hyaluronate, Phenoxyethanol, Laureth‐7, Ethylhexylglycerin, distributed by Medspa.
2.2. In vivo study design
The study was carried out according to the Helsinki declaration (Ethical Principles for Medical Research Involving Human Subjects). 18 A total of 30 healthy female volunteers between 25 and 64 years old with sensitive and dry skin were recruited according to the following general inclusion and exclusion criteria.
2.2.1. General inclusion criteria
Good general health.
Skin aging.
Sensitive and dry skin.
Absence of cutaneous diseases.
Absence of cutaneous lesions or other lesions in the area of interest that could interfere with the study evaluation.
No history of hypersensitivity to the common components of the cosmetic formulations.
Not pregnant or breastfeeding.
Subjects agreed not to undergo other treatments in the treated area for the entire duration of the test.
Subjects signed the informed consent form.
2.2.2. General exclusion criteria
Subjects that did not meet the inclusion criteria above.
Subjects undergoing pharmacological therapy.
Subjects that had participated in a similar study less than 60 days prior to the start of the present study.
Subjects with known allergies.
The study was carried out over 8 weeks following the half‐face experimental protocol active versus placebo. In this way, a comparison between the active and placebo product on the same subject was made in order to reduce as much as possible, the effect of unintentional factors other than treatment on the subject response. Each subject served as her own control, thereby giving greater statistical power to the study.
Methodology of the study: volunteers were trained to follow specific protocol of application.
Product: clean the area of interest with the provided cleanser and then apply the provide base cream twice a day in the morning and in the evening. Apply the serum (serum A or serum B) every other day in the evening (3 times a week) after cleansing; after 5 minutes of laying rinse with water and then apply the base cream.
Placebo: clean the controlateral area with the cleanser and then apply the cream twice a day in the morning and in the evening. Apply the serum placebo every other day in the evening (3 times a week) after cleansing; after 5 minutes of laying rinse with water and then apply the cream.
Volunteers were then divided into 2 different groups:
Group A was trained to apply serum A on one side of the face, and the placebo on the other side.
Group B was trained to apply serum B on one side of the face, and the placebo on the other side.
2.3. Instrumental efficacy evaluation
Assessments were performed at the beginning of each study (T0) after 4 weeks (T1) and at the end of the study, after 8 weeks (T2).
All measurements were made in an airconditioned room with controlled temperature and humidity (T = 22°C, relative humidity [RH] = 70 ± 5%). Subjects were preconditioned in the room for at least 15 minutes before the measurements were made.
The instruments used in the evaluation of skin parameters involve contact between the skin and a series of probes that do not cause discomfort, pain, or damage the skin.
2.3.1. Evaluation of tolerability and moisturizing effect
The tolerability was assessed by the measurement of the erythema index (EI) using a reflectance spectrophotometer (Mexameter MX 18, Courage & Khazaka), which measures levels of melanin and hemoglobin (erythema), the two components that are mainly responsible for the color of the skin. To make the measurement, a probe with a diameter of 5 mm emits three wavelengths of light (568, 660, and 870 nm) in order to quantify the amount of the selected biochromophores (melanin, hemoglobin), thus providing an arbitrary melanin index (MI; range = 0–999) and EI (range = 0–999).
Furthermore, the tolerability and the possible occlusive or irritant effect of the products used in this study were also evaluated by the assessment of skin barrier integrity, by the measurement of transepidermal water loss (TEWL). The assessment of TEWL (0 a 90 g/m2h) was performed by a skin evaporimeter made of a small cylindrical open chamber (1 cm in diameter, 2 cm in height) with a couple of hygrometric sensors connected to a microprocessor plugged into a computer workstation, using Tewameter TM 300 (Cutometer MPA580, Courage & Khazaka).
The acquisition of high‐resolution images of the skin surface by an optical method and complex mathematical algorithms to obtain images in three dimensions and measurement thanks to a dedicated software of topographic parameters, using a Antera 3D (Miravex Limited, Dublin, Ireland), was also performed to visualize the effect of the treatments.
The stratum corneum water content (SCWC), which reflects the hydrating effect of the product, was evaluated by a CM 825 corneometer (cutometer MPA580, Courage & Khazaka). Corneometry is a technique used to assess the hydration of the outer layer of the epidermis, which is known as the stratum corneum. 19 , 20 , 21 Since skin is a dielectric medium, all variations in hydration result in a corresponding change in the skin's electrical capacity. The device used in the present trial was equipped with a 49 mm2 surface probe that allows precise measurement in 1 second within a depth range of 10–20 μm in the stratum corneum. The parameters were expressed using an arbitrary score scale (0–100 A.U.).
2.3.2. Anti‐aging effect
Skin surface roughness
Skin surface roughness was evaluated using a PRIMOSpico instrument (GFM), which allows the acquisition of a 3D image of the skin surface by an optical analysis system and its transformation using dedicated software. 22 The 3D image acquired with the instrument can be transformed using specific software into a color image in which each shade of color (from blue to yellow) is related to a height; thus, the presence of a groove will be indicated by a color gradient that can transition from blue to green according to its depth. Parameters characterizing skin micro‐reliefs which can be measured at a glance thanks to this 3D topographic representation of the skin are the following:
Ra represents the average skin roughness. It is the integral of the function describing the skin roughness profile curve; the higher the value of Ra, the higher the skin roughness.
Rmax represents the maximal skin roughness. Single roughness depths are first determined by measuring the peak‐to‐valley distance within each evaluated sampling length. Rmax is the greatest peak‐to‐valley distance within any single sampling length, which is defined as the vertical distance between the top of the highest peak and the bottom of the lowest valley.
2.3.3. Firmness effect
Viscoelastic properties of the skin
The effect of the products on skin mechanical properties was evaluated using an MPA580 cutometer (Courage & Khazaka). In this technique, the skin is evaluated through the measurement of the vertical deformation of the skin induced by vacuum aspiration with a negative pressure of 450 mbar, which is applied to the skin for between 1 and 3 seconds through a probe with a diameter of 2 mm. 23 Each aspiration is followed by a release time, allowing the skin to return to its resting conditions. The considered parameters were: R0: Skin firmness. This parameter measures the maximum amplitude that the skin reaches following the application of suction by the cutometer and represents the passive response of the skin to applied force. R0 represents the ratio between skin looseness and skin tightness; the lower R0 is, the higher the firmness of the skin.
R2: the index represents the capability of the skin to return to its rest condition after being exposed to mechanical stress, that is, it is an index of the total elasticity of the skin. The closer R2 is to 1, the more elastic the skin is.
2.3.4. Purifying and renewal effect (PRBM)
Stratum corneum renewal effect
The stratum corneum renewal effect was investigated by the use of tape stripping, which is one of the most frequently used approaches to sample the stratum corneum. 24 This method involves the application of adhesive tape with a diameter of 14 mm (D101 D‐Squame Stripping Discs, Cuderm) to the skin, and its subsequent removal to strip off a layer of stratum corneum. A constant pressure of 225 g/ cm2 is impressed on the disk surface. The infrared densitometry (IRD) technique was used to quantify the absolute amount of stratum corneum removed by each tape strip.
In particular, a SquameScan™ device (CuDerm) was used to measure the protein content (PC) of the stratum corneum samples removed by tape stripping. This apparatus has a diode which emits light at a peak wavelength of 850 nm that shines through the tape strip onto a device which measures the amount of transmitted light. The results are expressed as PC in μg/cm2.
2.4. Statistical analysis
Data were processed both for descriptive statistical analysis and statistical analysis with comparison tests for parametric data. In particular, in the self‐controlled study methodology used in this work, a paired t‐test was applied. For each parameter analyzed in the clinical studies, a comparison was made between the values measured at time Ti (4 or 8 weeks) with respect to the initial value at time T0 and an evaluation of the net active‐placebo effect, for both group. A significance level of 5% was chosen, so changes were considered statistically significant for p < 0.05.
3. RESULTS
All volunteers used an active serum (serum A or serum B) on one half of the face and the same placebo serum on the other half of the face for the entire duration of the test. A randomized application procedure was applied.
3.1. Tolerability and moisturizing effect of products
The instrumental evaluation of the EI (erythema Index) can give information about product tolerability.
Table 1 reports the mean results from the erythema evaluation obtained from all volunteers at every scheduled time.
TABLE 1.
Mean data and mean variation of the erythema index in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B), and placebo (placebo‐group A and placebo‐group B)
| Timing | Mean | SD | VAR. % Ti‐T0 | p‐value | Significance |
|---|---|---|---|---|---|
| Serum A | |||||
| T0 | 311.49 | 43.84 | – | – | – |
| T4weeks | 309.46 | 43.63 | −0.63 | 0.0030** | Yes |
| T8weeks | 300.31 | 43.29 | −3.57 | ||
| Placebo‐Group A | |||||
| T0 | 308.48 | 37.89 | – | – | – |
| T4weeks | 305.93 | 34.05 | −0.68 | 0.7247 | No |
| T8weeks | 306.04 | 34.59 | −0.69 | ||
| Serum B | |||||
| T0 | 309.41 | 41.94 | – | – | – |
| T4weeks | 307.88 | 40.03 | −0.38 | 0.0006*** | Yes |
| T8weeks | 297.95 | 43.13 | −3.68 | ||
| Placebo‐Group B | |||||
| T0 | 307.86 | 40.55 | – | – | – |
| T4weeks | 305.33 | 39.73 | −0.78 | 0.5341 | No |
| T8weeks | 305.37 | 37.55 | −0.66 | ||
Note: *p < 0.05 is significant; **p < 0.01 is strongly significant; ***p < 0.001 is very strongly significant.
The investigated parameter decreases of about 3.5% after 8 weeks of products application (strongly statistically significant) both using serum A and serum B, thus both products are well tolerated and they are suitable for sensitive skin.
The confirmation of the tolerability of the products was obtain by the assessment of skin barrier integrity by the measurement of transepidermal water loss (TEWL).
Variations in TEWL values, reported in Table 2, were not significantly different in all tested groups, confirming that both products are well tolerated and they do not provoke damage to the skin barrier.
TABLE 2.
Mean data and mean variation of the transepidermal water loss (TEWL) in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B), and placebo (placebo‐group A and placebo‐group B)
| Timing | Mean | SD | VAR. % Ti‐T0 | p‐value | Significance |
|---|---|---|---|---|---|
| Serum A | |||||
| T0 | 10.15 | 1.06 | – | – | – |
| T4weeks | 10.38 | 1.25 | 2.67 | 0.7992 | No |
| T8weeks | 10.45 | 1.09 | 3.54 | ||
| Placebo‐Group A | |||||
| T0 | 10.01 | 1.04 | – | – | – |
| T4weeks | 10.24 | 1.35 | 2.71 | 0.5896 | No |
| T8weeks | 10.29 | 1.13 | 3.32 | ||
| Serum B | |||||
| T0 | 9.38 | 1.20 | – | – | – |
| T4weeks | 9.54 | 1.11 | 2.65 | 0.0674 | No |
| T8weeks | 9.79 | 1.33 | 4.56 | ||
| Placebo‐Group B | |||||
| T0 | 9.56 | 1.29 | – | – | – |
| T4weeks | 9.49 | 1.40 | −0.81 | 0.8717 | No |
| T8weeks | 9.57 | 1.33 | 0.23 | ||
Note: *p < 0.05 is significant; **p < 0.01 is strongly significant; ***p < 0.001 is very strongly significant.
Figure 1 shows a digital image of one volunteer of the group treated with ELPA25™ serum (Serum B) before and after treatment, in which the reduction of the redness is evident, confirming the good tolerability of the product.
FIGURE 1.
Digital images of the same area over time of one volunteer in the half face treated with ELPA25™ serum (Serum B) before (in the left) and after treatment (in the right)
Results obtained from the instrumental evaluation of hydration of stratum corneum are shown in the Tables 3 and 4.
TABLE 3.
Mean data and mean variation of the hydration of stratum corneum in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B) and placebo (placebo‐group A and placebo‐group B)
| Timing | Mean | SD | VAR. % Ti‐T0 | p‐value | Significance |
|---|---|---|---|---|---|
| Serum A | |||||
| T0 | 34.28 | 3.29 | – | – | – |
| T4weeks | 38.11 | 4.404 | 11.40 | <0.0001**** | Yes |
| T8weeks | 42.35 | 4.65 | 23.68 | ||
| Placebo‐Group A | |||||
| T0 | 33.17 | 3.95 | – | – | – |
| T4weeks | 35.49 | 3.71 | 7.38 | 0.0006*** | Yes |
| T8weeks | 35.69 | 4.76 | 7.73 | ||
| Serum B | |||||
| T0 | 32.12 | 4.71 | – | – | – |
| T4weeks | 38.66 | 6.00 | 20.49 | <0.0001**** | Yes |
| T8weeks | 43.61 | 7.21 | 36.14 | ||
| Placebo‐Group B | |||||
| T0 | 33.39 | 5.42 | – | – | – |
| T4weeks | 35.14 | 5.42 | 5.62 | 0.0004*** | Yes |
| T8weeks | 37.62 | 5.61 | 13.51 | ||
Note: *, P < 0.05 is significant; **, P < 0.01 is strongly significant; ***, P < 0.001 is very strongly significant.
TABLE 4.
Comparative analysis of the hydration of stratum corneum between active vs placebo in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B)
| Timing | p‐value | Significance |
|---|---|---|
| Group A | ||
| T0 product vs T0 placebo | 0.4794 | No |
| T1 product vs T1 placebo | 0.1086 | No |
| T2 product vs T2 placebo | 0.0006* | Yes |
| Group B | ||
| T0 product vs T0 placebo | 0.5878 | No |
| T1 product vs T1 placebo | 0.0975 | No |
| T2 product vs T2 placebo | 0.0128* | Yes |
Note: *p < 0.05 is significant; **p < 0.01 is strongly significant; ***p < 0.001 is very strongly significant.
Results highlighted that both Renewal Peel Serum based on ELPA25™ (Serum B) and Mandelic acid alone (serum A) improve the skin hydration obtained +20.49% and +11.40% in 4 weeks, +36.14% and +23.68% in 8 weeks, respectively.
Statistical analysis carried out on active area versus placebo area, as shown in the Table 3, permitted to eliminate the placebo effect evident after 4 weeks, and thus, it is possible to conclude that actives contained into both products exert skin moisturizing effect after 8 weeks of treatment.
3.2. Anti‐aging effect
The in vivo evaluation of the surface topography of human skin is of great interest for dermatological research because it reflects functional status of the skin, especially wrinkles and the variation in microrelief depth during aging. In order to assess the success of an anti‐aging treatment, parameters characterizing skin micro‐reliefs, such as Ra (the average skin roughness correlated to sensory perception) and Rmax (the greatest peak‐to‐valley distance in a single wrinkle), need to be measured before and after the application of the cosmetic product.
The greater the values of Ra and Rmax, the greater the skin roughness caused by skin texture, lines, and wrinkles.
The results obtained from the evaluation of roughness parameters of the skin are reported in the Table 5 and in the Figure 2.
TABLE 5.
Mean data and standard deviation of the texture parameters obtained from all volunteers in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B), and placebo (placebo‐group A and placebo‐group B)
| TIMING | Serum A Mean (±SD) | Placebo Group A Mean (±SD) | Serum B Mean (±SD) | Placebo Group B Mean (±SD) |
|---|---|---|---|---|
| Ra | ||||
| T0 | 31.47 (2.36) | 31.40 (3.02) | 33.40 (1.72) | 32.80 (2.57) |
| T4weeks | 30.27 (1.83) | 31.47 (2.83) | 28.87 (1.88) | 33.07 (2.58) |
| T8weeks | 28.87 (2.13) | 31.40 (2.67) | 27.27 (2.25) | 32.93 (3.08) |
| Rmax | ||||
| T0 | 237.93 (25.28) | 225.33 (27.50) | 243.93 (18.99) | 235.67 (25.58) |
| T4weeks | 215.13 (21.89) | 227.53 (24.68) | 212.73 (13.36) | 250.60 (25.84) |
| T8weeks | 207.53 (22.95) | 232.60 (29.13) | 194.47 (13.39) | 241.40 (22.51) |
FIGURE 2.
Mean variations and statistical analysis of the texture parameters (Figure A: Ra; Figure B: Rmax) obtained from all volunteers in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B) and placebo (placebo‐group A and placebo‐group B). *p < 0.05 is significant; **p < 0.01 is strongly significant; ***p < 0.001 is very strongly significant
Results highlighted that both serum are able to statistically reduce both skin texture parameters thus both serum exert anti‐age activity. In particular, Renewal Peel Serum based on ELPA25™ (Serum B) improves the skin texture (−13.49% of Ra in 4 weeks, −18.36% in 8 weeks) more than the mandelic acid alone (serum A) (−3.60% in 4 weeks, −8.13% in 8 weeks); furthermore, also the anti‐wrinkles effect of Renewal Peel Serum based on ELPA25™ (Serum B) (−12.44% in 4 weeks, −19.93% in 8 weeks) is higher than the efficacy obtained by mandelic acid alone (serum A) (−9.36% in 4 weeks, −12.53% in 8 weeks).
In both groups, the investigated parameters remain the same or get worse in areas treated with placebo serum.
The Figures below reported show, as an example, 3D overlapped images of same area over time obtained from the same volunteer. In particular, Figure 3 show picture captured from one volunteer in the half face treated with serum A and on the other half face treated with serum placebo; Figure 4 show picture captured from one volunteer in the half face treated with serum B and on the other half face treated with serum placebo.
FIGURE 3.
3D overlapped images of same area over time of one volunteer in the half face treated with serum A (Figure A: t0; t1; t2) and of the same volunteer in the other half face treated with serum placebo (Figure Pl: t0; t1; t2)
FIGURE 4.
3D overlapped images of same area over time of one volunteer in the half face treated with serum B (Figure B: t0; t1; t2) and of the same volunteer in the other half face treated with serum placebo (Figure Pl: t0; t1; t2)
3.3. Skin elasticity effect
The results obtained from the evaluation of mechanical properties of the skin are reported in the Table 6 and in the Figure 5.
TABLE 6.
Mean data and standard deviation of the Firmness (R0) and elasticity (R2) parameters obtained from all volunteers in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B), and placebo (placebo‐group A and placebo‐group B)
| TIMING | Serum A Mean (±SD) | Placebo Group A Mean (±SD) | Serum B Mean (±SD) | Placebo Group B Mean (±SD) |
|---|---|---|---|---|
| R0 | ||||
| T0 | 0.293 (0.047) | 0.247 (0.048) | 0.289 (0.058) | 0.238 (0.050) |
| T4weeks | 0.250 (0.050) | 0.263 (0.061) | 0.246 (0.065) | 0.257 (0.049) |
| T8weeks | 0.234 (0.040) | 0.266 (0.034) | 0.216 (0.055) | 0.260 (0.037) |
| R2 | ||||
| T0 | 0.507 (0.087) | 0.523 (0.090) | 0.498 (0.096) | 0.541 (0.079) |
| T4weeks | 0.550 (0.093) | 0.507 (0.073) | 0.570 (0.079) | 0.534 (0.122) |
| T8weeks | 0.542 (0.097) | 0.492 (0.104) | 0.639 (0.125) | 0.516 (0.095) |
FIGURE 5.
Mean variations and statistical analysis of the skin elasticity parameters (Figure A: R0; Figure B: R2) obtained from all volunteers in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B) and placebo (placebo‐group A and placebo‐group B). *p < 0.05 is significant; **p < 0.01 is strongly significant; ***p < 0.001 is very strongly significant
Results highlighted that both active products exerted a statistically significant positive effect both on skin firmness and on skin elasticity. In particular, Renewal Peel Serum based on ELPA25™ showed an higher effect on skin elasticity (+16.13% in 4 weeks, +29.25% in 8 weeks), to respect to serum made of mandelic acid alone (+9.11% in 4 weeks, +7.83% in 8 weeks).
3.4. Purifying and renewal effect
The tape stripping procedure is able to remove the first layers of the stratum corneum. At the beginning (T0), after 4 weeks and the end of the study (T8weeks), four different tape strippings were performed sequentially on the same area for each volunteer. Table 7 reports total tape stripping data expressed as Protein Content (PC) (μg/cm2).
TABLE 7.
Mean data and mean variation of the Protein Content (PC) in the areas treated with mandelic acid (Serum A), ELPA25™ serum (Serum B), and placebo (placebo‐group A and placebo‐group B)
| Timing | Mean | SD | VAR. % Ti‐T0 | p‐value | Significance |
|---|---|---|---|---|---|
| Serum A | |||||
| T0 | 24.38 | 6.57 | – | – | – |
| T4weeks | 24.17 | 6.41 | 0.75 | 0.0115* | Yes |
| T8weeks | 20.88 | 4.80 | −11.56 | ||
| Placebo‐Group A | |||||
| T0 | 23.49 | 6.44 | – | – | – |
| T4weeks | 23.14 | 5.41 | 0.18 | 0.4358 | No |
| T8weeks | 22.67 | 5.37 | −0.99 | ||
| Serum B | |||||
| T0 | 27.14 | 4.17 | – | – | – |
| T4weeks | 20.41 | 4.86 | −23.54 | 0.0002*** | Yes |
| T8weeks | 20.33 | 5.44 | −25.22 | ||
| Placebo‐Group B | |||||
| T0 | 21.95 | 3.94 | – | – | – |
| T4weeks | 22.04 | 3.40 | 1.43 | 0.5488 | No |
| T8weeks | 22.75 | 4.98 | 4.53 | ||
Note: *p < 0.05 is significant; **p < 0.01 is strongly significant; ***p < 0.001 is very strongly significant.
The results show that Renewal Peel Serum based on ELPA25™ led to a significant decrease of the average PC removed by tape stripping leading to an improvement in stratum corneum cohesion of 23.54% already in 4 weeks; this results suggests that this serum can exert a renewal effect on the epidermis through a mild exfoliating action. This effect can be attributable to the presence of gluconolactone that presents numerous hydroxyl groups which allows the molecule to work also as a humectant. This means that gluconolactone acts as an exfoliating acid, but also as a moisturizer.
The efficacy of Mandelic acid alone is half that of the Renewal Peel Serum based on ELPA25™ and only after 8 weeks of treatment (0.75% in 4 weeks, −11.56% in 8 weeks).
The variation of the average PC recovered in the placebo areas was not statistically significant.
4. CONCLUSIONS
The work proposes the new Miamo Renewal Peel Serum, formulated with a patent‐pending mixture of new generation acids (ELPA25™) specifically designed for sensitive skin.
Scientific protocol using self‐controlled study methodology and noninvasive skin bioengineering techniques with adequate statistical methods were successfully employed in order to discriminate both the efficacy of the two formulations tested (Renewal Peel Serum, based on ELPA25™ and mandelic acid serum) between them and with respect to placebo comparison.
Results obtained from 8 weeks in vivo study following the half‐face experimental protocol active versus placebo permitted to conclude that the combination of mandelic acid, gluconolactone, phytic acid, lactobionic acid, and Acetyl hexapeptide‐8 exert a very positive effect on sensitive skin. In fact, although both Renewal Peel Serum based on ELPA25™ and mandelic acid serum, used as control, demonstrated to be very tolerated and with a good hydrating efficacy, Serum based on ELPA25™ improves skin parameters more than the mandelic acid alone. Actually, the effects of Renewal Peel Serum based on ELPA25™ on skin texture and skin elasticity improvement and on reduction of wrinkles are higher than those obtained using mandelic acid alone.
In particular, only Renewal Peel Serum based on ELPA25™ led to a significant improvement in stratum corneum cohesion of 23.54% already in 4 weeks of treatment exerting a renewal effect on the epidermis through a mild exfoliating action, without any adverse effect.
In conclusion, this work confirmed that the pool of substances contained into Renewal Peel Serum based on ELPA25™ provides a synergistic action and thus it can be successfully used in sensitive skin.
AUTHOR CONTRIBUTIONS
G.G., P.P., and C.D. involved in conceptualization; P.P. involved in methodology and formal analysis; S.B. and P.P. involved in investigation; P.P. and G.G. involved in writing—original draft preparation; P.P., S.B., G.G., and C.D. involved in writing—review and editing; C.D. involved in supervision and project administration. All authors have read and agreed to the published version of the manuscript.
CONFLICT OF INTEREST
Camilla D'Antonio is co‐founder, stakeholder and scientific director of Medspa S.r.l. Giulia Gentili is an employee of said company where she works as a product manager. Medspa S.r.l. is an Italian company owner of the ELPA25™ trademark which is currently used for a cosmetic formulation. The patent application is pending.
ETHICAL APPROVAL
Authors declare human ethics approval was not needed for this study.
INFORMED CONSENT
Informed consent was obtained from all subjects involved in the study.
ACKNOWLEDGMENT
Open Access Funding provided by Universita degli Studi di Pavia within the CRUI‐CARE Agreement.
Gentili G, Perugini P, Bugliaro S, D’Antonio C. Efficacy and safety of a new peeling formulated with a pool of PHAs for the treatment of all skin types, even sensitive. J Cosmet Dermatol. 2023;22:517‐528. doi: 10.1111/jocd.15215
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.