Surg Today (2009) 39:587–591
DOI 10.1007/s00595-008-3944-y
Aloe Versus Silver Sulfadiazine Creams for Second-Degree Burns:
A Randomized Controlled Study
GHASEMALI KHORASANI1,6, SEYED JALAL HOSSEINIMEHR2,3, MOHAMMAD AZADBAKHT4, ARMAN ZAMANI1,
and MOHAMMAD REZA MAHDAVI5
1
Department of Surgery, Faculty of Medicine, 2 Department of Medicinal Chemistry, Faculty of Pharmacy, 3 Pharmaceutical Research Center,
4
Department of Pharmacognosy, Faculty of Pharmacy, and 5 Department of Clinical Laboratory, Faculty of Paramedical Sciences, Mazanda-
ran University of Medical Sciences, Sari, Iran
6
Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Purpose. Burn injury is associated with a high incidence
of death and disability; yet its management remains
problematic and costly. We conducted this clinical study
to evaluate the efficacy of aloe vera cream for partial
thickness burn wounds and compare its results with
those of silver sulfadiazine (SSD).
Methods. Thirty patients with similar types of second-
degree burns at two sites on different parts of the body
were included in this study. Each patient had one burn
treated with topical SSD and one treated with aloe
cream, randomly.
Results. The rate of re-epithelialization and healing of
the partial thickness burns was significantly faster in the
site treated with aloe than in the site treated with SSD
(15.9 ± 2 vs 18.73 ± 2.65 days, respectively; P < 0.0001).
The sites treated with aloe were completely healed in
less than 16 days vs 19 days for the sites treated with
SSD.
Conclusion. These results clearly demonstrated the
greater efficacy of aloe cream over SSD cream for treat-
ing second-degree burns.
Key words Burn · Aloe vera · Wound · Silver
sulfadiazine
Introduction
Despite the evolution of antiseptics, medications, and
advanced operative procedures, healing of burn injury
is still difficult to achieve.1 Burn injury is associated with
Reprint requests to: S.J. Hosseinimehr (address 2)
e-mail: sjhosseinim@yahoo.com
Received: July 22, 2008 / Accepted: November 28, 2008
6
Present address of G. Khorasani
a significant incidence of death and disability, multiple
operative procedures, prolonged hospitalization and
rehabilitation, and high health care costs. Many patients
exposed to thermal and boiling burn injury in Northern
Iran are hospitalized for lengthy treatment. More than
60% stay in hospital for 8–30 days.2 Burns are often
followed by sepsis, so topical antimicrobials are always
given prophylactically to prevent infective complica-
tions. The most common topical treatment for burn
injury is silver sulfadiazine (SSD) 1% cream because of
its antimicrobial efficacy.3 Delayed wound healing is the
most adverse effect of the silver topical agent. A study
examining the wound healing effects of SSD with gel
gauze in burned patients revealed that SSD delayed
wound healing.4 Moreover, adverse reactions and side
effects have been reported, such as resistance to SSD,
renal toxicity, and leukopenia: several studies confirmed
that this topical cream should not be used for long
periods on extensive wounds.5,6
Aloe vera (family: Liliaceae) has been used in tradi-
tional medicine for a long time. It is one of the most
recognizable herbs in the world and the medicinal part
is the succulent leaves. Leaf gel, leaf juice, fresh or dry
Aloe gel, obtained by breaking or slicing a leaf, are
principally used in herbal medicine. A topical skin gel
provides wonderful healing support for the skin. Aloe
vera contains many important nutrients for the body,
including amino acids, B vitamins, and other nutrients
that support general health. It also has pharmacologi-
cal properties including antioxidant, wound healing,
antibacterial, antifungal, and immunomodulating ef-
fects.7–14 Although burn wound healing is one of major
indications of aloe vera gel use in several animal and
clinical studies, few studies have compared the efficacy
of this gel with SSD in the treatment of burns in
patients.8
Realizing the potential use of aloe vera in wound
healing, we examined the effects of aloe vera cream
versus SSD on the rate of burn wound healing, indi-
588
cated by the burn wound size and re-epithelialization.
Silver sulfadiazine is used worldwide, even for second-
degree burn wounds; thus, we selected it as a control
from the viewpoint of clinical practice.
Materials and Methods
Aloe Vera
We applied pure spray-dried aloe vera powder
(Zarband Phytopharmaceutical, Tehran, Iran). This
product consists of the inner gel from plants and 150 g
of aloe vera powder was obtained from 30 l of filtrated
gel from the plants.
Preparation and Formulation of Aloe Cream
Liquid white paraffin 2 g, sterile alcohol 7.5 g, cetyl
alcohol 7.5 g, solid white paraffin 3 g, and propylene
paraben 0.015 g were mixed and heated to boiling point
as the oil phase. Aloe vera powder 0.5 g mixed with
70 ml deionized water was added to a mixture of pro-
pylene glycol 7 g, sodium lauryl sulfate 3 g, and methyl
paraben 0.025 g. The mixture was heated as the aqueous
phase. These two separate phases were mixed continu-
ously while being cooled. Thus, the uniform cream was
produced after cooling the cream filled in a plastic
package similar to an SSD box, weighing 500 g. The
cream contained aloe vera gel powder 0.5%. Our exper-
imental research and formulations were carried out
under sterile conditions. The final creams were tested
for any probable contamination microbes, which were
not detected during the applications.
Patients and Study Protocol
After obtaining approval from the Ethical Committee
at Mazandaran University of Medical Sciences, this
clinical trial was carried out in Zare’s Burn Hospital,
Iran. The inclusion criteria for the burned patients in
this study were as follows: the burn had to have occurred
within 24 h before the initiation of treatment; the patient
had to have two same site burns, such as on the feet or
hands; the burns had to be of second degree with respect
to depth and similar burned surface areas in two differ-
ent parts of the body; and the patients had to have less
than 40% total burn surface area (TBSA) burns. Exclu-
sion criteria included known diabetes, immunodefi-
ciency, pregnancy, and kidney diseases. Also excluded
were electrical and chemical burns. The patients and
attendants were given information regarding the drug
aloe cream and written informed consent was obtained
from all patients. Finally, 30 patients were enrolled in
this study.
G. Khorasani et al.: Effect of Aloe on Wound Healing
Table 1. Demographic characteristics
Characteristic Patients (n = 30)
Male/female 25/5
Mean ± SD age (years) 33 ± 11
% TBSA (range) 10–40
Mean ± SD TBSA 19.8 ± 7.9
Site of burn
Right and left hand 26 (87%)
Right and left foot 2 (7%)
Right or left hand 2 (7%)
Time until admission to hospital
<1 h 15 (50%)
1–3 h 12 (40%)
>3 h 3 (10%)
TBSA, total burn surface area
All patients were treated with fluid resuscitation,
daily dressings, and other treatment protocols during
their hospitalization. The age and sex distribution
pattern of patients is shown in Table 1. After admission,
the wounds were cleaned with water or normal saline
solution and the topical agent (aloe or SSD cream) was
applied directly to the wound in different parts; for
example, a left burned hand was treated with SSD and
the right burned hand was treated with aloe cream in
the same patient. The dressing was changed and creams
applied twice daily. Treatment with the topical agents
was continued until the burns were fully healed and
epithelialized. All patients were given oral nutrition
with occasional intravenous support in the form of
amino acid infusion and blood products during their
hospital stay. A wound swab culture was taken after 2
weeks. At the time of each dressing, the wound was
observed clinically for signs of infection, size, and rate
and nature of epithelialization by an expert surgeon. In
this study, the “B” part of the body was treated with
SSD and the “A” part was treated with aloe cream.
Patients and nursing staff were blinded to the proce-
dure. The length and width of the wound were mea-
sured with a ruler and photographed, and these
measurements were multiplied to calculate the area in
square centimeters. The healing percentage of the
wound and the healing time were recorded: the healing
percentage in the wound = [(area of first day-area of
second time)/(area at first time)] × 100.
Statistical Analysis
Data were analyzed by SPSS Win 10.0 (SPSS, Chicago,
IL, USA) software. The Student t-test and analysis of
variance test were used to compare the study groups,
wound size, and healing time. Significance level was
determined as less than 0.05.
G. Khorasani et al.: Effect of Aloe on Wound Healing 589

Table 2. Time of healing after treatment with silver sulfadia-

zine (ssd) vs. aloe creams
No. of patients
SSD group Aloe group
Time for complete healing (n = 30) (n = 30)

<10 days 1 2
<13 days 2 5
<16 days 7 25
<19 days 24 30
Healing (mean ± SD; days) 18.73 ± 2.65 15.9 ± 2
P value <0.0001

Fig. 1. Comparison of wound burn sizes in the silver sulfadia-

Results zine and aloe vera groups. The wound size was defined as
100% on day 4 and then calculated and compared with day 4
The demographic characteristics of the 30 patients with thereafter
burns at two sites are summarized in Table 1. Only
patients with partial thickness burns of the hands or feet
were selected, minimizing the number of factors such as
age, sex, and biological systems. The extent of partial
thickness burns and the size of the burn were the same
at both sites. With this randomization, one site was
treated with SSD cream and the other site was treated
with aloe cream. The mean times for healing were 18.73
± 2.65 and 15.9 ± 2 days for SSD and aloe creams,
respectively, being significantly shorter for aloe cream
(P < 0.0001; Table 2). The sites treated with aloe healed
approximately 3 days sooner than the sites treated with
SSD in all the patients. In fact, wound healing took less
than 16 days in 83% of the sites treated with aloe, but
more than 19 days in the sites treated with SSD. The
average wound size at 4, 7, 10, 13, 16, 19, 21, and 24 days
after burn injury are shown in Fig. 1. With this trend,
the percentage of each wound size was calculated by
reducing the fraction of the second to the first wound Fig. 2. Burns in a 45-year-old woman after 16 days of treat-
size (cm2). There was a significant difference between ment with silver sulfadiazine (left) and aloe (right) creams
the aloe group and the SSD group 10, 13, and 16 days
after treatment (P < 0.01).
The surfaces of both sites were swabbed to test for Visuthikosol et al.4 reported a study on 27 patients with
microbial contamination, and found to be negative on partial thickness burn wounds treated either with gauze
days 3, 7, and 13 (data not shown). Typical examples of dressings saturated with Aloe vera gel or other gel.
partial thickness burns treated with aloe and SSD dress- They observed significantly reduced wound healing
ings are shown in Fig. 2. time in the aloe-treated patients (11.19 days vs 11.89
days). In our study, the time taken for partial thickness
burns to heal was significantly shorter in the sites treated
Discussion with aloe than in those treated with SSD (15.9 ± 2 days
vs 18.73 ± 2.65 days). The antimicrobial effect of silver
The findings of this clinical study showed that aloe vera sulfadiazine is the only mechanism justifying its contin-
cream promoted burn wound healing more effectively ued use in burn injury. The silver ion binds with the
than SSD. The wounds treated with aloe were smaller DNA of an organism and releases the sulfonamide,
and took less time to heal. Although other studies have which kills microbes.17 Hepatic or renal toxicity and
shown aloe gel to be effective for burn wound healing leukopenia may be caused by the topical application of
in animal models and humans,4,9,15,16 they consisted of a SSD. In fact, these side effects have been observed in
few clinical trials and comparative studies on the effi- the treatment of large wounds.18,19 Although silver-
cacy of SSD as a common topical cream for burn injury.8 coated dressings have more advantages than topical
590
SSD, they can have adverse reactions and are very
expensive.20
Wound healing involves biological processes such as
inflammation and granulation tissue formation. Colla-
gen is the major protein in the extracellular matrix and
provides strength and integrity to the dermis and other
supporting tissues.21–23 Aloe vera enhances the produc-
tion of collagen.22 Glycoprotein fraction is the major
component of aloe to be involved in wound healing with
cell proliferation and migration.24 Isolated glycoprotein
fraction was found to promote the growth of dermal
fibroblasts, whereas neutral polysaccharide fraction
exhibited no such effects.25 The main mechanism of aloe
vera lies in how it acts on cell proliferation of the dermal
component. The glycoprotein fraction of aloe vera stim-
ulated cell proliferation, accelerated recovery of an arti-
ficial wound on the monolayer of normal keratinocytes,
and enhanced thickening of the epidermal covering.
This fraction stimulated both the fibroblasts and the
keratinocytes to produce fibronectin and its receptor.24
Another study found that aloe vera increased the col-
lagen content of the granulation tissue as well as the
degree of cross-linkage. It is thought that the enhanced
collagen content promotes stimulation by aloe in colla-
gen synthesis or increases the proliferation of fibroblast
synthesis of collagen, or both.26
The anti-inflammatory effects of aloe contribute to
the inflammatory process induced by burn injuries.25
Aloe may also reduce leukocyte adhesion and proin-
flammatory cytokines.27 Civelek et al.28 showed that a
low molecular weight heparin molecule, namely dalte-
parin, adversely affected incisional wound healing by
suppressing the early inflammatory process and increas-
ing cellular apoptosis.28 Infection is the major complica-
tion of skin burn injury, but this is inhibited by the
topical application of antimicrobial drugs. Silver sulfa-
diazine is effective in this regard, but aloe gel also has
antimicrobial effects11,14 and can reduce the risk of infec-
tion in burn injury of the skin. Muller et al.15 reported
that wound contraction was minimized by SSD. Aloe
vera, when added to SSD, reversed that effect in animals
and the half-life and healing times of the wounds were
shortest in the SSD+aloe vera groups and longest in the
SSD 1% group. These data show that aloe vera has
more synergistic effects than SSD alone in the treat-
ment of wound healing in animals.15
One of the main limitations of clinical trials is match-
ing patients in case and control groups, with a minimum
number of factors. The results of most such studies are
not creditable as a result of the poor matching of
patients. The findings of our study are supported by the
fact that it selected one patient with two burns of similar
size and type; one of each was treated with aloe and
SSD, thus eliminating the many parameters that would
cause alteration.
G. Khorasani et al.: Effect of Aloe on Wound Healing
In conclusion, aloe vera cream promoted wound
healing in burned patients better than SSD cream,
with smaller lesions and shorter healing times. The re-
epithelialization process was faster in the skin of patients
treated with aloe than in those treated with SSD. The
mechanism of the remarkable efficacy of aloe cream in
the healing of burn injuries may be explained by its
antimicrobial, cell proliferation, and inflammatory
effects.
Acknowledgment. This work was supported by a grant from
Mazandaran University of Medical Sciences, Sari, Iran. This
research was the subject of a thesis by Arman Zamani for an
MD degree in the Faculty of Medicine, Mazandaran Univer-
sity of Medical Sciences, Sari, Iran.
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