le-blinded comparative study between the use of glycolic acid 70% peel and the use of topical...

A single-blinded comparative study between the use of glycolic acid70% peel and the use of topical nanosome vitamin C iontophoresisin the treatment of melasma

Rehab Mohamed Sobhi, MD1 & Ahmed Mohamed Sobhi, MD2

1Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt2Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt

Summary Background Melasma is a common pigmentary disorder. Despite the availability of a wide

range of skin-lightening treatments, melasma of skin remains a therapeutic challenge.

Objective The aim of this study was to evaluate the efficacy and safety of nanosome

vitamin C iontophoresis and to compare the therapeutic effects of nanosome vitamin C

iontophoresis vs. glycolic acid peel 70% in the treatment of melasma in Egyptian

women.

Methods This study included 14 patients of melasma with skin type IV–V taken for a

right–left comparison study of six sessions. Glycolic acid 70% peel was applied on the

right side, whereas nanosome vitamin C was applied by iontophoresis on the other side.

The results are evaluated using the melasma area and severity index score and with

photographs at baseline and after six sessions. Also the photographs were evaluated by

two single-blinded physicians before and after sessions.

Results Both sides were improved, but the side treated with nanosome vitamin C showed

better results. Side effects were few and transient.

Conclusion We concluded that nanosome vitamin C is a new, safe and effective, easy and

painless method in the treatment of melasma.

Keywords: glycolic acid 70%, iontophoresis, melasma, nanosome vitamin C

mesosolution

Introduction

Melasma is a common pigmentary disorder character-

ized by the development of tan-brown macules and

patches. Chemical peeling is a popular method for

treating melasma and provides more rapid response to

topical treatment.1

Chemical peeling with glycolic acid 70% has been

used as safe and effective treatment for melasma in dark-

skinned persons.2 And it was found that glycolic acid

peel is a superior peeling agent than trichloroacetic acid

peel in the treatment of melasma.3

Vitamin C, a potent antioxidant and radical scavenger,

interferes with melanogenesis by inhibiting oxidative

reactions in the process of melanin formation.4 When

used as a monotherapy or in combination with other

agents, it lightens the skin.5 Companies like Skinceuti-

cals and La Roche-Posay have developed stabilized

vitamin C preparation. The stabilized preparation im-

proves hydration and reduces wrinkles, glare, and brown

spots, by reducing UV-induced collagen breakdown.6 In

a randomized, double-blinded, placebo-controlled study,

investigators used iontophoresis to enhance the pene-

tration of vitamin C into the skin and significantly

decreased pigmentation in patients with melasma.7

Correspondence: R M Sobhi, MD Department of Dermatology, Faculty of

Medicine, Cairo University, 87 (B) Abd El Azziz El Soued El Manial, Cairo,

Egypt. E-mail: [email protected]

Accepted for publication November 9, 2011

Journal Innoventions

Journal of Cosmetic Dermatology, 11, 65–71

� 2012 Wiley Periodicals, Inc. 65

The aim of this study was to evaluate the effect of

nanosome vitamin C iontophoresis as a safe and effective

method in the treatment of melasma as there are no

published data using the nanosome vitamin C mesoso-

lution as well as to compare the therapeutic effects of

melasma in Egyptian women treated with nanosome

vitamin C iontophoresis vs. glycolic acid peel 70%.

Patients and methods

This study included 14 patients with melasma with skin

type IV–V taken for a right–left comparison study of six

sessions. Complete history was taken from each patient,

and the data of the patients are summarized in Table 1.

Before each treatment, all patients were photographed,

and their faces were cleaned with 70% isopropyl alcohol.

Glycolic acid 70% peel (Delasco Company, Council

Bluffs, IA, USA, pH: 0.9, base vehicle: C3H4PO3), which

contains 70% glycolic acid, was applied on the right side

for 1–3 min or till the patients felt the burning sensa-

tion, then neutralized, whereas a few drops of C-VIT

Nano Meso Liposomal Solution (lipoceutical nano-

somes solutions; Lipoceutical nanosome & Technology

Sesderma, Valencia, Espania), which contained ascorbic

acid nanosomes, were applied by iontophoresis on the

left side. The machine was then moved gently until the

solution was absorbed by the skin, and a few more drops

were added till 0.5 mL of the solution was used. The

iontophoresis we used was ‘‘iontocare,’’ and we used the

negative mode, and the method used 50 mA in 10 min

which was calculated according to the equation:

dose = voltage · time (5 mA · 10 min = 50 mA)

(Fig. 1). Ascorbic acid nanosomes present in C-VIT

Nano Meso Solution are unilamelar, flexible, and with

an average size of 117.6 nm (±11.9 nm). Liposomal

solution is filtered through 200-nm cellulose membranes

(in a sterile atmosphere). Its composition is ascorbic

acid + protoglycans + vitamin A and E, and the vial

ingredients include aqua (water), 10% ascorbic acid,

alcohol denat, sodium cholate, tocopherol, sodium

hydroxide, sodium chloride, and phenoxyethanol. The

results are evaluated using the melasma area and

severity index (MASI score) and with photographs at

baseline and after six sessions.. The MASI score was

calculated for each patient at baseline and after six

sessions. The MASI was modified by Kimbrough-Green

et al.8 who based it on a scoring system similar to that

revised for psoriasis. Global evaluation of improvement

in response to therapy was done by the patient,

physician, and two blinded physicians at baseline

and at the end of sessions and was scored as marked

Table 1 Patient clinical data

Initial Age

Last delivery

years ago

CT pills

intake

Onset of

melasma Pattern

Previous

treatment Skin type Niqab

FA 33 6 No 6 Centrofacial No IV Yes

FM 35 3 No 3 Centrofacial Creams V NoNM 44 5 No 13 Centrofacial No V No

HB 41 2 No 17 Malar Yes IV No

BM 41 1 No 17 Centrofacial No IV No

RA 30 5 No 8 Centrofacial Creams IV No

MK 25 1 No 5 Malar Creams IV No

SA 47 24 No 5 Centrofacial Creams IV No

AM 45 35 No 12 Centrofacial Creams V No

SE 32 12 No 3 Malar Peeling IV No

MS 38 5 No 2 Malar No IV Yes

SO 50 27 No 20 Malar Creams V Yes

HS 47 0 No 3 Malar Creams IV No

EI 43 3 No 15 Centrofacial No V No

Figure 1 Iontophoresis of nanosome vitamin C on the left side.

66 � 2012 Wiley Periodicals, Inc.

Vitamin C nanosome iontophoresis melasma • R M Sobhi & A M Sobhi

(>75% improvement), very good (50% to <75%

improvement), good (25% to <50% improvement), or

poor (<25% improvement). All patients were instructed

to use sunscreens between sessions.

Statistical methods

Data were statistically described in terms of

mean ± standard deviation (±SD), frequencies (number

of cases), and percentages (%) when appropriate. Quan-

titative variables between the study groups were com-

pared using Student’s paired t-test. For comparing the

categorical data, Pearson’s chi-square test was per-

formed. P < 0.05 was considered statistically signifi-

cant. All statistical calculations were performed using

Microsoft Excel 2007 (Microsoft Corporation) and

SPSS (Statistical Package for the Social Sciences; SPSS

Inc., Chicago, IL, USA) version 17 for Microsoft

Windows.

Results

Patient’s data

Fourteen women were enrolled in this study with age

ranging from 25 to 50 years, with a mean age of

39.36 ± 7.397. The duration of melasma ranged from 2

to 20 years, with a mean of 9.21 ± 6.253. Patient skin

phototype was Fitzpatrick IV in nine patients (64.3%)

and V in 5 (35.7%). Three of these patients were

wearing niqab (21.4%). The melasma pattern was

centrofacial in eight patients (57.1%) and malar pattern

in 6 (42.9%). The time since last delivery by the women

ranged from 0 to 35 years, with a mean of

9.21 ± 11.164 years. All our patients continued the

six sessions except for one patient who received five

sessions because her leg was broken during the study.

Evaluation and analysis of MASI score

The average MASI score before treatment on the right

side was 7.9714 ± 2.536, whereas after treatment, it

changed to 6.2143 ± 2.725; thus, the average decrease

in MASI score was 1.757. Thus, the treatment of MASI

on the right side had a 22.042% decrease, and this was

statistically significant (P = 0.001 with 95% (CI) of their

difference 0.859–2.655). On the left side, the average

MASI score before treatment was 8.3143 ± 2.815,

whereas after treatment, it changed to 4.778 ± 2.793;

thus, the average decrease in MASI score was 3.535.

Thus, the treatment of MASI on left side had a 42.519%

decrease, and this was statistically significant

(P < 0.000 with 95% (CI) of their difference 1.887–

5.185).

Of the two sides, the left side showed significantly

more reduction in MASI score than the right side

(Fig. 2). On comparing, the P value of MASI score

between right and left side before treatment was 0.738

and after was 0.180, which means that both sides

showed clinical improvement as there was reduction in

MASI score on both sides, but the reduction was more

on the left side and it was statistically insignificant.

Analysis of global evaluation

The global evaluation at the end of sessions on the right

side was poor in one patient, good in eight, very good in

three, and excellent in two patients; on the left side, it

was good in two, very good in seven, and excellent in

five (Figs 3 and 4, Table 2). The photographs were

assessed by two blinded physicians, blinded physicians 1

and 2, and their evaluations are summarized in Tables 2

and 3. The side effects observed are summarized in

Table 4.

Discussion

Glycolic acid 70% penetrates the stratum corneum,

provokes rapid epidermolysis, and can lead to the

mechanical removal of the epidermis. Some authors

have demonstrated improvement in melasma with 70%

glycolic acid and Jessner solution.9 Hurley et al.10 did

not show improvement in melasma with the application

of a sequence of peelings with glycolic acid at 20% and

30%. Lim and Tham11 demonstrated improvement in

melasma after a sequence of eight peelings of glycolic

acid at concentrations of 20–70% and was only

Figure 2 Melasma area and severity index score on both sides

showing better reduction on the left side.



observed after the initiation of the 70% glycolic acid

peelings. Glycolic acid was studied to be an effective and

safe therapy, either alone or as part of a combination

treatment to reduce the MASI.12,13

l-Ascorbic acid affects the monophenolase activity of

tyrosinase14, thus reducing melanin synthesis. Also, it

has a photoprotective effect, preventing the absorption of

UV rays.15 It is retained in the epidermis, which is an

advantage over sunscreens that are easily removed.16 It

has an antioxidant effect, preventing the production of

free radicals that trigger melanogenesis. It also mini-

mizes oxidized melanin, changing the pigmentation from

black to tan;17 vitamin C was used as a sole agent in the

treatment of melasma in a double-blind randomized

study vs. hydroquinone (4%) with good results and was

well tolerated with less irritation than hydroquinone.18

Iontophoresis increases drug penetration into the

tissue as a result of an applied current through the

tissue.19 It has been regarded as a very promising

treatment modality because it offers the possibility of

controlled delivery of drugs and is potentially effective

for any charged molecule.20 Chien et al.21 suggested

that the electrical potential gradient induces changes in

the arrangement of lipid, protein, and water molecules.

(a)

(b)

(c)

(d)

Figure 3 (a) Patient before nanosome vitamin C iontophoresis (left cheek), (b) Same patient after treatment showing very good

improvement, (c) Same patient before glycolic acid 70% peel on the right cheek, (d) Same patient after six sessions of glycolic acid peel 70%

with poor improvement.



The structural changes caused by the electrical current,

such as micropore formation in the stratum corneum,

may assist the transport of charged drugs across the

stratum corneum.22

In our study, the side treated with glycolic acid 70%

showed moderate improvement in melasma; similar

results were obtained by Silonie,3 confirming that

glycolic acid peel is safe and effective in the treatment

(a)

(b)

(c)

(d)

Figure 4 (a) Patient before nanosome vitamin C iontophoresis (left cheek), (b) Same patient after treatment showing very good

improvement on the left side, (c) Same patient before glycolic acid peel 70% on the right cheek, (d) Same patient after six sessions peel with

glycolic acid showing poor improvement.

Table 2 Physician and patient global evaluation

Improvement

Physician Patients

Right side Left side Right side Left side

Poor (<25%) 6 (42%) 3 (21.4%) 1 (7.1%) 0

Good (25–50%) 3 (21.4%) 3 (21.4%) 8 (57.1%) 2 (14.3%)

Very good (50–75%) 5 (35.7%) 3 (21.4%) 3 (21.4%) 7 (50%)

Excellent >75% 0 5 (35.7%) 2 (14.3%) 5 (35.7%)

P value 0.090 0.058

Table 3 Evaluation of blinded physicians 1 and 2

Improvement

Physician 1 Physician 2

Right side Left side Right side Left side

Poor (<25%) 4 (28.6%) 2 (14.3%) 2 (14.3%) 1 (7.1%)

Good (25–50%) 4 (28.6%) 1 (7.1%) 7 (50%) 4 (28.6%)

Very good (50–75%) 2 (14.3%) 5 (35.7%) 3 (21.4%) 6 (42.9%)

Excellent >75% 4 (28.6%) 6 (42.9%) 2 (14.3%) 3 (21.4%)

P value 0.245 0.503



of melasma and this was statistically significant. On the

side treated with nanosome vitamin C, there was marked

improvement in melasma, but there are no published

data using the nanoformulation and iontophoresis

and our study is the first using nanosome vitamin C

and iontophoresis. Huh et al.7 showed that vitamin

C iontophoresis is an effective treatment for melasma. On

comparing the two sides, nanosome C showed signifi-

cantly more reduction in MASI score than the glycolic

acid side.

The P value of MASI score between right and left side

before treatment was 0.738 and the P value of MASI

after was 0.180, which means that both sides showed

clinical improvement as there was reduction in MASI

score on both sides, but the reduction was more on the

left side and this was statistically insignificant, which

may be explained by the fewer number of patients.

Subjective evaluation of the patients revealed that 12

(85.5%) of them showed very good to excellent response

on the left side, whereas 5 (36.1%) showed very good to

excellent response on the right side. Huh et al.7 used

topical vitamin C iontophoresis and showed marked

improvement; but our study is the first study using

nanosome C solution delivered to the skin by iontopho-

resis. Thus, we conclude that nanosome vitamin C

iontophoresis is an easy and safe method in the

treatment of melasma, convenient, painless way for

drug delivery, and also that even though glycolic acid

70% peel is effective in the treatment of melasma,

nanosome vitamin C iontophoresis showed more

improvement as shown by the higher decrease in MASI

score on the side treated with nanosome vitamin C.

References

1 Sarkar R, Kaur C, Bhalla M, Kanwar A. The combination

of glycolic acid peels with a topical regimen in the treat-

ment of melasma in dark-skinned patients: a comparative

study. Dermatol Surg 2002; 28: 828–32.

2 Khunger N, Sarkar R, Jain RK. Tretinoin peel versus

glycolic acid peels in the treatment of melasma in dark

Skinned Patients. Dermatol Surg 2004; 30: 756–60.

3 Sachovela S. Comparative efficacy of 10–20% trichloro-

acetic acid and 35–70% glycolic acid peel in 60 cases of

melasma, freckles, lentigines and postinflammatory hyper-

pigmentation. J Pak Assoc Dermatol 2006; 16: 74–8.

4 Ros JR, Rodriguez-Lopes JN, Garcia-Canovas F. Effect of

L-ascorbic acid on the monophelase activity of tyrosinase.

Biochem J 1993; 295: 309–12.

5 Sherdin U, Filbry A, Scholermann A, Rippke F. Skin light-

ening products for patients with facial melasma. Eur

Dermatol 2010; 5: 68–73.

6 Humbert PG, Haftek M, Creidi P et al. Topical ascorbic acid

in photoaged skin. Clinical topographical and ultrastruc-

tural evaluations: double blinded study vs placebo. Exp

Dermatol 2003; 12: 237.

7 Huh CH, Seo K, Park JY et al. A randomized, double-blind,

placebo-controlled trial of vitamin C iontophoresis in

melasma. Dermatology 2003; 206: 316–20.

8 Kimbrough-Green CK, Griffiths CEM, Finkel LJ et al. Topical

retinoic acid (tretinoin) for melasma in Black patients.

A vehicle-controlled clinical trial. Arch Dermatol 1994;

130: 727–33.

9 Lawrence N. Treatment of melasma with Jessner’s solu-

tion versus glycolic acid: a comparison of clinical efficacy

and evaluation of the predictive ability of Wood’s light

examination. J Am Acad Dermatol 1997; 36: 589–93.

10 Hurley ME, Guevara IL, Gonzales RM, Pandya AG. Efficacy

of glycolic acid peels in the treatment of melasma. Arch

Dermatol 2002; 138: 1578–82.

11 Lim JTE, Tham SN. Glicolic acid peels in the treatment of

melasma among Asian women. Dermatol Surg 1997; 23:

177–9.

12 Rendon M, Cardona LM, Bussear EW et al. Successful

treatment of moderate to severe melasma with triple-com-

bination cream and glycolic acid peels: a pilot study. Cutis

2008; 82: 372–8.

13 Sezer E, Erbil H, Kurumlu Z et al. A comparative study of

focal medium-depth chemical peel versus cryosurgery for

the treatment of solar lentigo. Eur J Dermatol Jan–Feb,

2007; 17: 26–9.

14 Kameyama K, Sakai C, Kondoh S et al. Inhibitory effect of

magnesium l-ascorbyl-2-phosphate (VC-PMG) on melano-

genesis in vitro And in vivo. J Am Acad Dematol 1996; 34:

29–33.

15 Dreher F, Maibach H. Protective effects of topical

antioxidants in humans. Curr Probl Dermatol 2001; 29:

157–64.

16 Darr D, Combs S, Dunston S et al. Topical vitamin C

protects porcine skin from ultraviolet radiation induced

damage. Br J Dermatol 1992; 127: 247–51.

17 Catani MV, Rossi A, Costanzo A et al. Induction of gene

expression via activator protein 1 in ascorbate protection

against UV-induced damage. Biochem J 2001; 15: 77–85.

18 Espinal-Perez LE, Moncado B, Castanedo-Cazares JP.

A double-blind randomized trial of 5% ascorbic acid vs.

4% hydroquinone in melasma. Int J Dermatol 2004; 43:

604–7.

Table 4 Side effects reported

Side effects

Peeled side

(right side)

Vitamin C side

(left side)

Mild sense of electric shock 0 1

Blister 4 0

Burning sensation 1 1

Dryness of face 1 0Postinflammatory hyperpigmentation 2 0



19 Lee SH, Choi EH, Feingold KR et al. Iontophoresis itself on

hairless mouse skin induces the loss of the epidermal

calcium gradient without skin barrier impairment. J Invest

Dermatol 1998; 111: 39–43.

20 Green PG, Flanagan M, Shroot B, Guy RH. Iontophoretic

drug delivery. In: Walkers KA, Hadgraft J eds. Pharmaceu-

tical Skin Penetration Enhancement. New York: Dekker;

1993: 311–33.

21 Chien YW, Siddiqui O, Shi WM et al. Direct current ionto-

phoretic transdermal delivery of peptide and protein

drugs. J Pharm Sci 1989; 78: 376–84.

22 Grimmes S. Pathways of ionic flow through human

skin in vivo. Acta Derm Venereol (Stockh) 1984; 64:

93–8.



le-blinded comparative study between the use of glycolic acid 70% peel and the use of topical...

Documents