A novel hydrogel‐based moisturizing cream composed of hyaluronic acid for patients with xerosis: An intraindividual comparative analysis

Abstract

Background

Hyaluronic acid (HA) is mainly used to treat xerosis. It also exerts wound‐healing, moisturizing, and antiaging effects. Although HA is considered an effective and safe ingredient in cosmetics, there is a constant demand for a more money‐saving and effective formulation. This study aimed to evaluate the safety and efficacy of a novel hydrogel‐based moisturizer containing HA cross‐linked with silicone polymers, produced solely through irradiation without the use of cross‐linking agents.

Materials and Methods

A safety study enrolled 30 participants with healthy skin to perform patch and photopatch tests while recording adverse events. For the efficacy study, 30 participants with xerosis were compared before and after using the novel hydrogel, evaluating the cutaneous barrier function, xerosis severity scale (XSS) score, participant's satisfaction, and Investigator's Global Assessment (IGA). Furthermore, the efficacy of the novel hydrogel‐based moisturizer was evaluated by comparing it with a conventional moisturizer, Physiogel, in another 30 participants with xerosis.

Results

In the safety study, no serious adverse events were observed. In the efficacy study before and after use, skin hydration and skin surface lipid increased (p < 0.05) whereas the XSS scores decreased (p < 0.05) with time. In the comparative efficacy study with Physiogel, skin hydration increased whereas the XSS scores decreased (p < 0.05) over time in both groups. Furthermore, IGA improved in 100% of participants in both groups. Also, 100% and 93% of participants were satisfied with the novel hydrogel‐based moisturizer and Physiogel, respectively.

Conclusions

The novel hydrogel‐based moisturizer proved to be safe and effective for xerosis, showing comparable results to the conventional moisturizer.

1. INTRODUCTION

Xerosis is a condition caused by decreased hydration of the stratum corneum and is characterized by various clinical signs, including microscopic cracks, scaling, and inflammation in the skin. ¹ , ² It significantly impairs patients’ quality of life, particularly causing itching. ³ It may be caused by external or environmental factors and endogenous factors, such as physiological and hormonal changes related to aging. ⁴ , ⁵ , ⁶ However, the most crucial causative factors are decreased function of keratinocytes and low moisture and lipid contents of the stratum corneum. ⁷ The basic skin care for xerosis includes enhancement of skin hydration, compensation for the lack of barrier lipids, and improvement of the cutaneous barrier function. The products used for skin care include lipophilic components for lipid replenishment and hydrophilic components for rehydration, such as glycerin, urea, and hyaluronic acid (HA). ⁸ HA is a safe substance used in cosmetics and various other medical applications; it also exerts wound‐healing, moisturizing, and antiaging effects. ⁹ Substances such as HA form the ingredients of hydrogel and are used according to various medical needs. In general, hydrogels are produced by adding cross‐linking agents to polymer materials. However, as these cross‐linking agents exert carcinogenic, neurotoxic, and mutagenic effects, ¹⁰ residual cross‐linking agents must be removed during the manufacturing process, which incurs additional production costs. However, SKINMED Inc. (Daejeon, South Korea) recently developed a new biocompatible hydrogel‐based moisturizer containing HA and silicone polymers (Table 1), which was produced solely through irradiation without using cross‐linking agents; it is anticipated to be nontoxic and incur lesser production costs. This study aimed to evaluate the safety of the moisturizer formulated using the novel hydrogel by conducting patch and photopatch tests. In addition, the efficacy of the novel hydrogel‐based moisturizer was assessed by measuring its effects before and after application. This study also investigated the comparative efficacy of the novel hydrogel‐based moisturizer and a conventional moisturizer, namely, Physiogel Prop Intensive Cream MD (Stiefel Laboratories, Inc., Middlesex, UK). The efficacy was evaluated through various measures, such as the cutaneous barrier function test, xerosis severity scale (XSS) score, participant's satisfaction, and Investigator's Global Assessment (IGA).

TABLE 1.

Ingredients of the novel hyaluronic acid‐based hydrogel.

List of all components
Water
Caprylic/Capric Triglyceride
Glycerin
Dipropylene Glycol
Cetearyl Alcohol
Stearic Acid
Hydrogenated Lecithin
Ceramide NP
Sodium Hyaluronate
1,2‐Hexanediol
Hyaluronic Acid/Silicone Crosspolyme (tentative name)
Centella Asiatica Extract
Squalane
Methyl Glucose Sesquistearate
Glycine Soja (Soybean) Sterols
Behenyl Alcohol
Panthenol
Tremella Fuciformis (Mushroom) Extract
C14‐22 Alcohols
Arachidyl Alcohol
Cetyl Palmitate
Sorbitan Olivate
Sorbitan Palmitate
C12‐20 Alkyl Glucoside
Arachidylglucoside
Polyacrylate Crosspolymer‐6
Hydroxyethyl Acrylate/Sodium Acryloyldimethyl Taurate Copolymer
Ethylhexylglycerin
Citric Acid
Sodium Citrate
Trisodium EDTA
Sorbitan isostearate
Glucose
Fragrance

2. MATERIALS AND METHODS

2.1. Participants

The safety study enrolled 30 participants aged over 20 years with healthy skin, whereas the efficacy study enrolled 60 participants aged over 50 years who were diagnosed with xerosis. Women who were pregnant, nursing, or planning to become pregnant, participants who received treatment with oral and topical steroids and topical ointment for calcineurin inhibition within 4 weeks prior to the study, and participants who were allergic or sensitive to cosmetics and ultraviolet‐A (UV‐A) were excluded from the study. Concurrent administration of other medications during the study period was prohibited.

2.2. Methods

2.2.1. Study protocol for safety evaluation

The participants were asked about basic characteristics, such as sex, age, height, weight, smoking history, and drinking history as well as skin type, moisture, oil, and sensitivity, average sleep time, and average UV exposure time at the first visit. Skin type was identified as oily, neutral, dry, problematic, or combination skin. Furthermore, skin hydration was categorized as insufficient, moderate, or moisturized and skin oiliness as insufficient, moderate, or very oily. Skin sensitivity was classified into easily stimulated, stinging, itching, or other adverse events. To evaluate safety, a comparative study was performed in which patch and photopatch tests were conducted on the right and left arms of a participant. The novel hydrogel‐based moisturizer was applied to the participant's right upper arm as a treated group. On the other hand, only HA, a constituent of the novel hydrogel (1.5‐MDa NaHA), was applied to the participant's left upper arm as a control group (100 mg of novel hydrogel‐based moisturizer and 0.04 mL of HA for each test). The patch test was conducted using IQ chambers (Chemotechnique Diagnostics AB, Sweden) and was assessed 2‐ and 4‐days following substance application. In the photopatch test, UV‐A at a dose of 5 or 10 J/cm² was irradiated 2 days following substance application. Then, the response was reexamined after 2 days of UV‐A irradiation. The study protocol was approved by the Institutional Review Board (IRB) of Kyungpook National University Hospital (IRB no. KNU 2021‐11‐021). Written informed consent was obtained from all of the participants before the study initiation. The study was conducted at our hospital between January 3 and 14, 2022.

2.2.2. Study protocol for assessing efficacy

The efficacy of the novel hydrogel‐based moisturizer was compared before and after use in a group of 30 participants with xerosis. Another group of 30 participants with xerosis was included to compare the efficacy of the novel hydrogel‐based moisturizer with that of the conventional moisturizer, Physiogel Prop Intensive Cream MD. At the initial visit, all the participants answered a questionnaire containing items about basic characteristics, including skin conditions. For the evaluation before and after use, the novel hydrogel‐based moisturizer was applied to one shin of the participants twice daily in the morning and evening in the amount of one index finger. To compare its efficacy with that of Physiogel, the novel hydrogel‐based moisturizer was applied to the right shin of the participants, whereas the control substance, Physiogel, was applied to the participant's opposite shin in the same manner. The experiment was conducted with double‐blinding. The participants revisited the hospital 2, 4, and 8 weeks later; skin xerosis assessment and cutaneous barrier function test were performed at every visit. Each participant visited between 1:00 PM and 6:00 PM for evaluation, consistently arriving at the same time. The cutaneous barrier function was calculated after relaxing for 30 min in an indoor area with a temperature of 24°C−26°C and humidity of 40%−60%. The study protocol was approved by the IRB of Kyungpook National University Hospital (IRB no. KNU 2022‐01‐025 and 2022‐07‐018). Written informed consent was obtained from the participants before the study initiation, and the study was conducted at our hospital from March 14, 2022, to November 11, 2022.

2.2.3. Safety evaluation

Based on the criteria of the Frosch and Kligman method, ¹¹ skin response to patch and photopatch tests was examined (score 0 = no reaction; score 0.5 = rarely detectable erythema; score 1 = slight erythema; score 2 = moderate uniform erythema; score 3 = intense edematous erythema; and score 4 = intense edematous erythema with vesicles). The average reaction was estimated using the following equation and interpreted based on the Cosmetic, Toiletry, and Fragrance Association (CTFA) Safety testing guidelines (Table 2) ¹² :

$$\mathrm{Response}=100\times \frac{\sum \left(\mathrm{number}\mathrm{of}\mathrm{responders}\times \mathrm{score}\right)}{\mathrm{N}\left(\mathrm{total}\mathrm{participants}\right)\times 4\left(\mathrm{maximum}\mathrm{score}\right)}$$

TABLE 2.

Human primary irritation index for cosmetic products.

Range of response (R)	Criteria
0.00 ≤ R < 0.87	Slight
0.87 ≤ R < 2.42	Mild
2.42 ≤ R < 3.44	Moderate
3.44 ≤ R	Severe

2.2.4. Efficacy evaluation

The participants’ satisfaction was rated on a 5‐point scale (1 = dissatisfied to 5 = very satisfied. The investigator examined skin dryness using XSS (Table 3) and conducted cutaneous barrier function tests and IGA. As the skin barrier function tests, we determined transepidermal water loss (TEWL), skin hydration, skin surface lipids, skin surface pH, color (erythema and melanin), and smoothness using Tewameter, Corneometer, Sebumeter, Skin‐pH‐meter, Mexameter, and Frictiometer, respectively (Courage & Khazaka GmbH, Cologne, Germany). IGA was rated on a 6‐point scale (0 = clear; 1 = excellently improved; 2 = moderately improved; 3 = slightly improved; 4 = did not improve; 5 = worse).

TABLE 3.

Xerosis severity scale.

Mild	0	Normal skin
	1	Dusty appearance, occasional minute skin flakes
	2	Generalized dusty appearance, many minute skin flakes
Moderate	3	Defined scaling with flat borders
	4	Well‐defined heavy scaling with raised borders, shallow fissures
Severe	5	Large‐scale plates, fissures
	6	Large‐scale plates, deep erythematous fissures

2.2.5. Adverse events

Any adverse events that occurred during the study period were documented, which were subjectively described by the participants and objectively examined by the investigators.

2.3. Statistical analysis

Repeated measures analysis of variance, paired t‐test, and Wilcoxon's signed‐rank test were adopted to evaluate the distinctions in the XSS scores and the cutaneous barrier function using the SPSS software (version 18.0, SPSS, Inc., Chicago, IL, USA). p < 0.05 was considered to indicate statistical significance.

3. RESULTS

3.1. Basic characteristics of the participants of the safety study

Of the 30 participants, 12 were men, and 18 were women, and their mean age was 46.1 ± 14.3 years. Regarding skin type, 13 participants had dry skin; 8, neutral; 8, oily; and 1, combination; no participant had problematic skin type. A total of 12 participants mentioned a lack of skin moisture, and no participant had moist skin. Of all the participants, seven (23.3%) had skin irritations, nine (30.0%) had stinging sensation, and three (10.0%) had adverse reactions. Table 4 presents the other characteristics.

TABLE 4.

Basic characteristics of the participants of the safety study (n = 30).

Item	Classification	Frequency (n)	Percentage (%)
Skin type	Dry	13	43.3
	Neutral	8	26.7
	Oily	8	26.7
	Combination	1	3.3
	Problematic	0	0.0
Skin moisture	Moisturized	0	0.0
	Moderate	18	60.0
	Insufficient	12	40.0
Skin oiliness	Very oily	4	13.3
	Moderate	20	60.7
	Insufficient	6	20.0
Sleep time per day	<5 h	1	3.3
	Between 5 and 8 h	24	80.0
	>8 h	5	16.7
UV exposure time per day	<1 h	7	23.3
	Between 1 and 3 h	15	50.0
	>3 h	8	26.7
Smoking	No	26	86.7
	<10 pieces	0	0.0
	>10 pieces	4	13.3
Irritability	Yes	7	23.3
	No	23	76.7
Stinging	Yes	9	30.0
	No	21	70.0
Adverse events by cosmetics	Yes	3	10.0
	No	27	90.0

3.2. Participants’ subjective assessment of safety

After the patch and photopatch tests, a subjective evaluation for tingling, burning, and itching sensations was performed. In both the treated and control groups, five and two participants reported slight itching 30 min and 48 h after the patch removal, respectively. In the photopatch test with 5 J/cm² UV‐A, one participant reported mild itching after 1 h of patch attachment, five after 30 min of patch removal, and two after 48 h of patch removal; no significant difference was observed between the treated and control groups. The photopatch test with 10 J/cm² UV‐A (Table 5) had similar outcomes.

TABLE 5.

Participants’ subjective assessment of skin irritation in the safety study (n = 30).

		Patch test
		1 h after the patch test		30 min after removal		48 h after removal
Symptom	Grade	Experimental	Control	Experimental	Control	Experimental	Control
Tingling	No	30	30	30	30	30	30
	Mild	0	0	0	0	0	0
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0
Burning	No	30	30	30	30	30	30
	Mild	0	0	0	0	0	0
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0
Itching	No	30	30	25	25	28	28
	Mild	0	0	5	5	2	2
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0

Photopatch test (UV‐A 5 J/cm2)
		1 h after the patch test		30 min after removal		48 h after removal
Symptom	Grade	Experimental	Control	Experimental	Control	Experimental	Control
Tingling	No	30	30	30	30	30	30
	Mild	0	0	0	0	0	0
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0
Burning	No	30	30	30	30	30	30
	Mild	0	0	0	0	0	0
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0
Itching	No	29	29	25	25	28	28
	Mild	1	1	5	5	2	2
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0

Photopatch test (UV‐A 10 J/cm2)
		1 h after the patch test		30 min after removal		48 h after removal
Symptom	Grade	Experimental	Control	Experimental	Control	Experimental	Control
Tingling	No	30	30	30	30	30	30
	Mild	0	0	0	0	0	0
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0
Burning	No	30	30	30	30	30	30
	Mild	0	0	0	0	0	0
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0
Itching	No	29	29	25	25	28	28
	Mild	1	1	5	5	2	2
	Moderate	0	0	0	0	0	0
	Severe	0	0	0	0	0	0

3.3. Investigator's assessment of safety

According to the Frosch and Kligman method, skin response was determined 30 min and 48 h after the patch removal. In the patch test, the average reactivity was 0 in both the treated and control groups. In the photopatch test with UV‐A 5 J/cm², the average reactivity of the treated group was 0, whereas that of the control group was 0.21. In the photopatch test with UV‐A 10 J/cm², the average reactivity of the treated group was 0.63, whereas that of the control group was 0.83. According to the CTFA guidelines, all responses were determined to exhibit the lowest reactivity (slight) (Table 6).

TABLE 6.

Investigator's assessment of skin irritation in the safety study (n = 30).

		Patch test
		30 min after removal						48 h after removal
Group	No. of patient	0.5	1	2	3	4	R	0.5	1	2	3	4	R	Mean of R (Criteria)
Experimental	0	–	–	–	–	–	0	–	–	–	–	–	0	0 (Slight)
Control	0	–	–	–	–	–	0	–	–	–	–	–	0	0 (Slight)

		Photopatch test (UV‐A 5 J/cm2)
		30 min after removal						48 h after removal
Group	No. of patient	0.5	1	2	3	4	R	0.5	1	2	3	4	R	Mean of R (Criteria)
Experimental	0	–	–	–	–	–	0	–	–	–	–	–	0	0 (Slight)
Control	1	1	–	–	–	–	0.42	–	–	–	–	–	0	0.21 (Slight)

		Photopatch test (UV‐A 10 J/cm2)
		30 min after removal						48 h after removal
Group	No. of patient	0.5	1	2	3	4	R	0.5	1	2	3	4	R	Mean of R (Criteria)
Experimental	3	3	–	–	–	–	1.25	–	–	–	–	–	0	0.63 (Slight)
Control	4	3	–	–	–	–	1.25	1	–	–	–	–	0.42	0.83 (Slight)

R: reactivity.

3.4. Basic characteristics of the participants of the efficacy study

In the efficacy study before and after use, among the 30 participants with xerosis, 11 were men and 19 were women, and their average age was 57.8 ± 5.2 years. Eight participants (26.7%) reported having easily irritated skin, three (10.0%) have had stinging, and five (16.7%) have had adverse reactions from cosmetics. In the study comparing efficacy between Physiogel and the novel hydrogel‐based moisturizer, among the 30 participants diagnosed with xerosis, 13 were male, and 17 were female, and their average age was 56.2 ± 3.2 years. Six participants (20.0%) reported having easily irritated skin, whereas two (6.7%) reported stinging sensations, and two (6.7%) have had adverse reactions to cosmetics. Table 7 presents the other characteristics.

TABLE 7.

Basic characteristics of the participants of the efficacy study (n = 60).

		Before and after use (n = 30)		Comparing with Physiogel (n = 30)
Item	Classification	Frequency (n)	Percentage (%)	Frequency (n)	Percentage (%)
Sleep time per day	<5 h	1	3.3	2	6.7
	Between 5 and 8 h	27	90.0	21	70.0
	>8 h	2	6.7	7	23.3
UV exposure time per day	<1 h	3	10.0	1	3.3
	Between 1 and 3 h	21	70.0	17	56.7
	>3 h	6	20.0	12	40.0
Smoking	No	28	93.3	23	76.7
	<10 pieces	0	0.0	1	3.3
	>10 pieces	2	6.7	6	20.0
Irritability	Yes	8	26.7	6	20.0
	No	22	73.3	24	80.0
Stinging	Yes	3	10.0	2	6.7
	No	27	90.0	28	93.3
Adverse events by cosmetics	Yes	5	16.7	2	6.7
	No	25	83.3	28	93.3

3.5. Efficacy before and after use

Before and after using the novel hydrogel‐based moisturizer for 2, 4, and 8 weeks, the investigator conducted a visual assessment of xerosis. Figure 1 presents the average and standard deviations of the XSS scores over the course of the study period. The use of the novel hydrogel‐based moisturizer for an 8‐week duration resulted in a significant decrease in the XSS scores when compared with the pre‐application measurement (p < 0.05). Figure 2 shows a graphical representation of the average values and standard deviations of Tewameter, Corneometer, Sebumeter, Skin‐pH‐meter, Mexameter (M = melanin; E = erythema), and Frictiometer before and after the use of the novel hydrogel‐based moisturizer. No significant change was observed in Tewameter before and after use. After application of the novel hydrogel‐based moisturizer for 8 weeks, statistically significant increases were observed in Corneometer, Sebumeter, and Frictiometer compared with their respective baseline measurements (p < 0.05). At 8 weeks of using the novel hydrogel‐based moisturizer, a significant decrease was observed in Skin‐pH‐meter and Mexameter(M, E) (p < 0.05). However, the results were consistently maintained at a similar level throughout the study period.

FIGURE 1.

A significant reduction in the xerosis severity scale (XSS) scores was observed after the application of the novel hydrogel‐based moisturizer (p < 0.05). Data are expressed as means ± standard deviation.

FIGURE 2.

Changes in the results of the cutaneous function test in response to the novel hydrogel‐based moisturizer application. Data are expressed as means ± standard deviation. (A) No significant change was observed in transepidermal water loss compared with the baseline measurement. (B) The level of skin hydration measured using Corneometer increased with time (p < 0.05). (C) The measurement of skin surface lipids using Sebumeter showed a time‐dependent increase (p < 0.05). (D) Over time, the mean values of Skin‐pH‐meter decreased (p < 0.05). (E, F) The mean values of Mexameter (M, E) decreased over time (p < 0.05). (G) The mean values of Frictiometer tended to increase over time (p < 0.05).

3.6. Comparison of efficacy between Physiogel and the novel hydrogel‐based moisturizer

Figure 3 presents the XSS scores for the novel hydrogel‐based moisturizer and Physiogel groups, whereas Figure 4 shows Tewameter, Corneometer, Sebumeter, Skin‐pH‐meter, Mexameter (M, E), and Frictiometer for both groups. The mean XSS score in both the novel hydrogel‐based moisturizer and Physiogel groups statistically significantly decreased over time (p < 0.05). Furthermore, no significant differences were observed between the two groups. At weeks 2, 4, and 8, TEWL changes were statistically insignificant and irregular compared with baseline in both groups (Figure 4A). The mean values of Corneometer significantly increased over time (p < 0.05) in both groups (Figure 4B). The mean values of Sebumeter initially increased and then decreased at week 8, remaining higher overall than the pre‐use levels (Figure 4C). The values of Skin‐pH‐meter showed irregular changes in the novel hydrogel‐based moisturizer group and slightly decreased in the Physiogel group (Figure 4D). Furthermore, the Mexameter (M, E) mean value significantly decreased over time (p < 0.05) in both groups (Figure 4E,F). The mean values of Frictiometer increased over time in the Physiogel group compared with the novel hydrogel‐based moisturizer group (Figure 4G). The outcomes of Corneometer and Frictiometer significantly differed between the groups (p < 0.05), whereas other measurements had similar changes with no significant differences.

FIGURE 3.

Decrease in the xerosis severity scale (XSS) scores in the novel hydrogel‐based moisturizer and Physiogel groups after the application (p < 0.05). Data are expressed as means ± standard deviation.

FIGURE 4.

Changes in the cutaneous function test results after the application of the novel hydrogel‐based moisturizer and Physiogel. Data are expressed as means ± standard deviation. (A) Transepidermal water loss exhibited irregular changes over time in both the novel hydrogel‐based moisturizer and Physiogel groups without a significant difference between the groups. (B) The skin hydration levels, measured using Corneometer, increased over time in both the novel hydrogel‐based moisturizer and Physiogel groups. A significant difference was observed between the groups (p < 0.05). (C) The skin surface lipid levels, measured using Sebumeter, showed a tendency to increase over time in both groups, with no significant difference between the groups. (D) The mean values of Skin‐pH‐meter showed irregular changes over time in the novel hydrogel group and decreased in the Physiogel group. (E, F) The mean values of Mexameter (M, E) decreased over time in both groups. (G) The mean values of Frictiometer tended to increase over time in both groups, with a significant difference between the groups (p < 0.05).

3.7. IGA and participant satisfaction of novel hydrogel‐based moisturizer comparing with Physiogel

The IGA of the novel hydrogel‐based moisturizer and Physiogel groups is presented in Figure 5A,B. In the novel hydrogel‐based moisturizer group, improvement was observed in 93%, 100%, and 100% of the participants after 2, 4, and 8 weeks of application, respectively. In the Physiogel group, improvement was observed in 97%, 100%, and 100% of the participants after 2, 4, and 8 weeks of application, respectively. Figure 5C,D present the participants’ satisfaction levels in both the novel hydrogel‐based moisturizer and Physiogel groups. The findings indicate that among all the participants, the novel hydrogel‐based moisturizer group had satisfaction rates of 73%, 97%, and 100% after 2, 4, and 8 weeks of application, respectively. On the other hand, the Physiogel group had satisfaction rates of 63%, 93%, and 93% over the same duration, respectively.

FIGURE 5.

Investigator's Global Assessment at the visit after 2, 4, and 8 weeks in the (A) novel hydrogel‐based moisturizer group and (B) Physiogel group. Participant's satisfaction at the visit after 2, 4, and 8 weeks in the (C) novel hydrogel‐based moisturizer group and (D) Physiogel group.

3.8. Adverse events

No serious adverse events were documented.

4. DISCUSSION

Approximately 60% of the human body is composed of water, which keeps the skin moist and shiny. ¹³ The stratum corneum has a thickness of 0.06−1.00 mm and contains 10%−20% of the total water content. When the hydration level in the corneal layer decreases below 10%, the skin becomes dry and rough, which cause skin barrier problems, thereby increasing the amount of moisture loss to the environment. ¹⁴ The moisturizing power of weakened skin can be enhanced through cosmetics, which not only hydrate the surface of the stratum corneum but also reduce TEWL. ¹⁵ Moisturizers that are extensively used include glycerin, HA, and sealed moisturizers, such as silicone and mineral oils. ¹⁶

HA is a nonsulfated linear glycosaminoglycan polymer with repeating disaccharide units of D‐glucuronic acid N‐acetyl‐d‐glucosamine linked through β−1,4‐glycosidic bonds. ¹⁷ , ¹⁸ It is mainly present in the extracellular matrix, and the cutaneous HA accounts for more than 50% of the total HA in the body. ¹⁷ Commercially available HA can be obtained from animal sources or bacteria fermentation or produced through chemoenzymatic synthesis. ¹⁹ , ²⁰ Owing to its biocompatibility, unique viscoelasticity, nonimmunogenicity, and biodegradability, HA has been used on the skin to exert antiaging, tissue regenerating, rejuvenating, and hydrating effects. In particular, HA is able to hold water up to 1000 times its own volume; thus, it can hydrate both the epidermis and dermis. ²¹

At present, several studies are being conducted to determine the mechanism of action and biosynthesis of HA and are focusing on maximizing its biotechnological production to synthesize derivatives with exceptional properties and increase their therapeutic utilization. ⁹ HA is widely used not only in cosmetics as a cosmetic additive, owing to its outstanding biocompatibility and high solubility in solution, but also in various pharmaceutical applications. ²² These applications include its use as an ophthalmic surgical adjuvant, an enhancer of joint function, a drug delivery medium, and an ingredient in eye drops. ²² However, the utility of HA is significantly constrained by its inherent vulnerability to degradation in vivo or under conditions such as exposure to acidic or alkaline environments. ²³ Consequently, it is common to add chemical crosslinking agents in the production of HA‐based hydrogels. ²²

In contrast, in the case of HA, its molecular weight and viscosity decline due to degradation reactions induced by exposure to radiation. ²⁴ Therefore, the development of HA‐based hydrogels produced solely through radiation exposure, without the addition of chemical crosslinking agents or organic chemicals, has been challenging. To address this challenge, the present study incorporates another biocompatible polymer, polyethylene glycol (PEG), in conjunction with HA. ²⁵ This hybrid approach facilitates the creation of a biocompatible hydrogel based on HA that is generated solely through radiation exposure, thus eliminating the requirement for chemical crosslinking agents or organic compounds.

PEG has many advantages in the field of drug delivery and tissue engineering. ²⁶ It is characterized by its high solubility in organic solvents, non‐toxicity, lack of immune responses, and excellent biocompatibility. ²⁶ It can easily encapsulate and release drugs, making it a valuable material in the pharmaceutical industry. ²⁷ Additionally, PEG is used in contact with blood because it enhances the biocompatibility of polymers used in blood‐contacting applications and has a significant protein adsorption inhibition effect. ²⁷ As a result, PEG finds numerous applications in the field of biomaterials.

Yoo, et al. conducted an experiment to determine the extent to which HA‐PEG hydrogel can swell in different solvents. ²⁵ Hydrogels were prepared by subjecting a mixture of 1% 100 kDa HA and 1% 20 kDa PEG to 100kGy of electron beam irradiation. These hydrogels were then freeze‐dried to ensure uniform size. Subsequently, they were placed in various solvents, including water, saline solution, phosphate‐buffered saline (PBS), dimethyl sulfoxide, methanol, dimethylformamide, ethanol, and tetrahydrofuran, and their size and weight were monitored over a period of up to 10 h. The results showed that HA‐PEG hydrogel rapidly absorbed most solvents, reaching its maximum weight within 5 min. However, the extent of swelling varied depending on the type of solvent. It was observed that the hydrogel exhibited the highest swelling in water, followed by saline solution and PBS, indicating that the HA‐PEG hydrogel has a strong swelling capacity in water‐based solvents. This outcome can be attributed to the exceptional water retention capability of HA within the HA‐PEG hydrogel.

In this study, the novel hydrogel was produced by SKINMED Inc. through the induction of intermolecular or intramolecular crosslinking between HA and/or PEG molecules by subjecting the HA and PEG mixture to electron beam irradiation. The percentage of cross‐linked polymer in the newly developed moisturizer was 3%. We assessed the safety and efficacy of this novel moisturizer in actual clinical settings and compared its efficacy with that of Physiogel Prop Intensive Cream MD. Not only does it increase skin moisture and inhibit the loss of moisture from the skin like conventional moisturizers, but it is also cost‐effective owing to mass production via irradiation.

Among the participants of the safety study, two (6.7%) complained of mild itching in both the treated and control groups 48 h after the patch and photopatch tests with 5 and 10 J/cm² UV‐A. Although some participants reported mild itching, no difference was observed between the two groups. Therefore, it cannot be considered as a significant adverse event of the experimental material. Furthermore, the mean reactivity of skin irritation evaluated by the investigator ranged from 0 to 0.63 in the treated group (skin irritation level = mild). Zerbinati N. et al. injected a hydrogel made of cross‐linked polyethylene glycol and HA into the skin, and consequently, hypoallergenic reaction and minimal discomfort were reported. ²⁸

The efficacy study of the novel hydrogel‐based moisturizer showed an improvement in xerosis and an increase in skin moisture and oil content. When efficacy was compared between Physiogel and the novel hydrogel‐based moisturizer, there was no significant change in TEWL, but skin moisture content increased, skin oiliness tended to increase, skin acidity remained similar, and erythema and pigment slightly decreased. Although Physiogel increased skin moisture to a greater extent than the novel hydrogel‐based moisturizer, no difference was observed between the two substances in terms of TEWL, skin oil content, and erythema and pigment. It is believed that the novel hydrogel‐based moisturizer is efficient in increasing skin hydration and sebum level, which are crucial for cutaneous barrier function. ²⁹ , ³⁰ Furthermore, for both substances, skin acidity was between 4 and 6, which are pH values indicating a healthy skin ³¹ ; however, the novel hydrogel‐based moisturizer maintained a value similar to that of Physiogel. The friction values of the skin increased after using both materials but increased to a greater extent with Physiogel than with the novel hydrogel‐based moisturizer. Therefore, it was confirmed that the novel hydrogel‐based moisturizer is not inferior to Physiogel Prop Intensive Cream MD, which is extensively used in the market.

Conclusively, the novel HA‐based hydrogel evaluated in this study is a safe, efficient, and cost‐effective moisturizer for xerosis.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

Ha NG, Kim SL, Lee SH, Lee WJ. A novel hydrogel‐based moisturizing cream composed of hyaluronic acid for patients with xerosis: An intraindividual comparative analysis. Skin Res Technol. 2023;29:e13499. 10.1111/srt.13499

DATA AVAILABILITY STATEMENT

Data Availability Statement, and if applicable, included functional and accurate links to said data therein.