Dandruff
and Chemo-Antidandruff Agents
Sushant Sharma1,
Minakshi Shroff1*, Yashwant
Swarnakar2, Mamta Singh1 and Ashish Pandey1
1Institute of
Pharmacy, Chhatauna, Mandir
Hasaud, RITEE, Raipur, Chhattisgarh, India
.2Shri Sankaracharya Institute of Pharmaceutical Sciences,
Chhattisgarh, India.
*Corresponding Author E-mail: mahishroff@gmail.com
ABSTRACT
Dandruff is often seen in the primary care setting as
well as in the dermatology field. In this article, we review the mostly used
drugs for treating dandruff and compare their efficacy in eradicating the
symptoms of dryness and flaking of the scalp, along with providing relief of
associated pruritus. Examples of such agents include keratolytics, regulators of keratinization,
antimicrobials, and naturopathic therapies. We examine their mechanisms of
action and their efficacy in treating dandruff.
KEYWORDS: Dandruff, Antidandruff agent,
Dermatology.
INTRODUCTION:
Term
“Dandruff”- pityrasis, meaning bran-like
epidermal scaling (Greek pityron: bran-like) was introduced into dermatological
vocabulary by Galen. [1] Disease constitutes a vary widespread
problem, present in more than a half of population of Caucasian origin.[2]
.Although most commonly it is a problem of just aesthetic nature chronic
character of this condition and tendency to relapse makes it troublesome and
difficult to cope for people suffering from this condition.
Causative organism:
a) Pityriasis simplex
b) Pityriasis steatoids
c) Malassezia furfur
d) M. restricta
e)
M. Globosa
Types of dandruff:
Two types of dandruff can occurs – common (dry) or oily
dandruff. [3]
Common (dry) Dandruff: (Pityriasis simplex
capiliti S. sicca, furfuracea) is characterised by
excessive formation of minute scales of whitegreyish
or ashen colour, accumulating on the scalp area.
These bran-like scales are first localised in the
middle of the scalp area and then spread towards, parietal, frontal and
occipital areas.[3]
Scales visible on the scalp are separated cells of keratinised layer, whose renewal cycle is pathologically
shortened (even to 7 days, with the normal equalling
28 days). Hairs in this type of dandruff are not changed and no hair loss is
observed.
In the epidermis of people suffering from
common dandruff histopathology analysis reveals characteristic intervals of parakeratosis foci, raised mitotic index of corneocytes and peeling in the form of multicellular
aggregates; there is no actual inflammatory status of the proper skin.[4]
Oily
Dandruff: (Pityriasis steatoides ), being just the form of dandruff arising on
the scalp skin with varied intensity of sebum production. It appears most often
in young men following puberty (aged between 18 and 24). On the skin of the
scalp area inflammation of various intensity then develops, constituting the
basis for basis for fragile, oily scales (pityraisis oleosa) of dirty yellow colour,
which can be associated with pruritus of various
intensity.[3]
Severity of
Dandruff:
Sometimes, dandruff can be extreme and
difficult to treat. Extreme dandruff is often causes by a condition called “seborrheic dermatitis” which has a build-up of skin cells
in scaly patches on the scalp. In babies, “seborrheic
dermatitis” is referred to as “cradle cap.”
Some medical causes for extreme dandruff
are:
·
Seborrheic dermatitis: This condition is distinguished
by oily and red skin and can show up on the scalp as well as other oily parts
of the body. On the scalp, dead skin cells will form a crusty layer appearing
yellow or white in color. These dead skin cells may attach to the hair
follicles. In babies and toddlers, it is commonly referred to as “cradle cap.”
·
Psoriasis:
Dead skin cells do not shed and leave the skin surface as they should. The
result is a buildup of dead, hard skin forming scales.
·
Eczema: Sensitive skin with dry red rash. Eczema,
if located on the scalp, can make the scalp very sensitive and itchy.
·
Malassezia: A yeast-like fungus, malassezia occurs on most adult’s scalps without causing any problems. In some
cases, the malassezia may grow out of control and
being to feed on the oil secretions by the hair follicles. This can cause
excess dead skin cells to mix with the oil and form clumps which are very
visible on clothing.
·
In
severe cases of dandruff, for which the medical term is seborrheic
dermatitis or seborrhea, some hair follicles could be damaged or destroyed. But
there is no evidence in the medical journals that baldness is caused by
ordinary dandruff. Dandruff and baldness often occur together though. Many
people assume from this that one is caused by the other. It's a false
assumption.
Etiology of Dandruff:
The aetiology of dandruff,
being the form of seborrhoeic dermatitis, is not unequivocally established Many
factors are usually listed, described as endogenous and exogenous. Researchers
include the following into the first group
1. Endogenous: (i) Immunological abnormalities, related
to humoral and cell immunity, proved by associated
severe sebhorrhoeic dermatitis often observed in
subjects infected with HIV or suffering from AIDS; disorder is present in a
significant proportion of this group of patients (34-83%);[5]
(ii) Neurological abnormalities (during depression,
also in case of Parkinson disease),
2. Exogenous: (i) Life style (incorrect
skin care , micro trauma and stress ),
(ii)Diet factor (poor nutrition, alcoholism) (iii)Environmental factors
(environmental pollution and climate).[5,6,7]
Seborrhoeic dermatitis can also be associated with the
presence of other disease including: pancreatitis, HVC infection, neoplasm and
also genetic abnormalities (for example down syndrome, hailey-hailey
disease).[5]
a) Microbial etiology of dandruff
There could be several etiopathologic pathways with complex mechanisms, which may
cause dandruff. The role of lipophilic yeast
belonging to the genus malassezia was widely accepted
to play a role in dandruff way back in 1846.[12,14] Eichstedt was the first to recognize the presence of this fungus in the disease pityriasis versicolor.[8,15] The scalp form as biocenose for various organisms such as Staphylococci spp., Propionibacterium
spp., and Malassezia
spp.,[16,17] The density of these organisms varies from
10 3 to 10 5 organisms per mm 2 . During
dandruff, the levels of Malassezia increase by 1.5 to 2 times its normal level. It has
been debated that the quantitative microbial assessment of all kinds does not
indicate the role of yeast; the abundance that might have been proportional to
the volume of scales which it colonizes or be responsible for the altered
desquamation. Interestingly, the specific relationship between a species of Malassezia
appears to be the strategy for treating dandruff.
In response to the use of antifungal preparations, population of Malassezia
reduces, but the bacterial population is seldom affected. After withdrawal of
treatment, the clinical situation recurs and Malassezia population
increases to the initial level. Another interesting aspect on the microbial
cause of dandruff is the positive treatment response of dandruff to various
steroids. Steroids are known to suppress the immune flare-up and the microbe
will advantageously utilize the immune suppressed opportunity. But the good
treatment response and prolonged remission period with steroid treatment raises
a doubt on the microbial cause of dandruff. Whether the increased Malassezia
count is the result of abundant scales or abundant scales is due to the
increased Malassezia
population lack clear explanation till date.[16] There are seven species of Malassezia - M. globosa, M. resticta, M. obtuse, M. sloofiae, M.
sympodialis, M. furfur and M. pachydermatis, which have been
recognized in dandruff formation.[18]
However, none of the species of Malssezia have fulfilled the
Koch's postulates as a pathogen of dandruff till date.
b) Non-microbial
etiopathology of dandruff:
The non-microbial cause for
dandruff is well established. Excessive exposure to sunlight is known to cause
desquamation of the scalp.[19,20] Minimal irritation of scalp due to
over shampooing, frequent combing, use of certain cosmetic products, dusts and
dirt also, to some extent, cause dandruff. However, there is no sufficient
experimental evidence to the above assumptions.[21]
Detail
discussion: Dandruff:
Pathophysiology:
Even today, the debate on
whether dandruff has to be treated as a disease or a disorder continues. In the
physiological spectrum of scaling, about 487,000cells/sq cm get released
normally after detergent treatment and this number goes up to 800,000/sq cm
during dandruff and seborrhoeic dermatitis.[8] However, dandruff is
non-inflammatory in nature. The real cause for dandruff formation from the
normal physiological spectrum of scaling is yet to be understood.
The spectrum of dandruff is
difficult to define because its blurs with seborrhoeic dermatitis and some
other scaly conditions. The inflammation and extension of scaling outside the
scalp excluded the diagnosis of dandruff from seborrhoeic dermatitis.[9] However,
many reports suggest a clear link between the two clinical entities – the
mildest form of the clinical presentation of seborrhoeic dermatitis as
dandruff, where the inflammation is minimal and remain subclinical.
Histological examination reveals the scattered presence of lymphoid cells and
squirting capillaries in the papillary dermis with hints of spongiosis
and focal parakeratosis.[10,11]
Conceptually, dandruff is a
dander and represents nothing more than physiological scaling.[12] Hence
it is believed that physiological scaling process requires more cosmetic
management. The response to treatment is commonly swift, but transient. On the
contrary, seborrhoeic dermatitis is obviously more inflammatory in nature
extending outside the limit of the scalp surface.[8]
Composition:
Dandruff scale is a cluster
of corneocytes, which have retained a large degree of
cohesion with one another and detach as such from the surface of the stratum corneum. The size and abundance of scales are heterogeneous
from one site to another and over time. Parakeratotic
cells often make up part of dandruff. Their numbers are related to the severity
of the clinical manifestations, which may also be influenced by seborrhea.[13]
Causes:
The most common cause of dandruff is the fungus Malassezia
furfur (previously known as Pityrosporum
ovale). This fungus is found naturally on the skin
surface of both healthy people and those with dandruff. The fungus feeds off of
sebum and is consequently found most on skin areas with many sebaceous glands:
on the scalp, face and upper part of the body. When Malassezia
furfur grows too rapidly, the natural renewal of
cells is disturbed and dandruff appears with itching. Mild dandruff may be
caused by overactive sebaceous glands which are triggered by hormonal imbalance
or stress.
Other causative factors include family history, food
allergies, excessive perspiration, use of alkaline soaps and yeast infections.
Even the season of the year can contribute to the problem. Cold, dry winters
are notorious for bringing on dandruff or making it worse. Symptoms of dandruff
can also be aggravated by exposure to dust, UV light, harsh shampoos and hair
dyes. [22]
Nature:
Research suggests that dandruff is a subclinical
inflammatory scalp disorder resulting in a disruption of connection between the
cells within the top layer of the skin. This abnormality may only be episodic,
but can also be a permanent condition. Often such kind of mild scalp
inflammation is accompanied by varying degrees of pruritus.
The dandruff scale is an aggregate of horny skin cells which have retained a
large degree of cohesion with each other and become detached in clusters from
the surface of the upper layer of the skin. The size of the scales is
heterogeneous at a given site of the scalp, and their abundance may vary from
one site to another and over time. [23]
Role
of corneocytes in dandruff:
Both in dandruff and
seborrhoeic dermatitis, the population of malassezia
is not uniform throughout the skin surface and inside the stratum corneum.[10,24] Clumpy adherence of the yeast is
seen in some corneocytes, whereas other corneocytes in the neighborhood region harbor few of these
yeast. It is presumed that perhaps the Malassezia binding site may
differ in corneocytes. Another postulate is the
natural antifungal peptides of the innate immunity to the above cause. The
colonization of the yeast boosts the expression of β-defensin-2 by keratinocytes.[25] In dandruff, their expression
could be impaired at some sites where the abundance of Malassezia is more. It is
known that Malassezia
has antigenic and pro-inflammatory properties stimulating both innate and
acquired immune response and neuro immune sensorial
response as well.[26] In
dandruff, the immune response is not altered.
The Malassezia
- corneocyte hypothesis still leaves some doubt. It
does not explain why scaling at low grade (2-5 mg/cm scalp/2 days) with low parakeratotic index persist despite dandruff being resolved
and Malassezia
largely removed.[8] It is
hypothesized that the antifungal agents may not be able to eradicate deep-seated
yeasts allowing a minimal inflammatory reaction to be maintained or the anti
inflammatory activity claimed in the antidandruff agents is not effective
enough in vivo.[27]
The adverse reaction such as irritant dermatitis or contact allergic dermatitis
may be provoked by the treatment agents also. [28]
Human scalp is very androgen
sensitive and sebum rich.[8,29] The sebum forms an ideal nutrient in
the biocenose and sebum formation starts with the
onset of puberty. However, sebum excretion rate in dandruff infected and
non-infected subjects was found to be same. Many subjects with oily scalp did
not show dandruff as well.[30] This clearly shows that lipids may
facilitate to some extent but not be the primary cause. Many authors presume
that host susceptibility factors play a major role in dandruff formation. It is
already known that skin surface lipids influence the transient form of M. orbiculare and M. furfur. It is also known that dandruff affects
people at puberty and middle age more than elderly subjects.[12] In
vitro findings suggest that cholesterol and cholesterol esters induce hyphal formation in Malassezia.
However, the quantitative or qualitative difference in skin lipids in pityriasis infected and non-infected subjects doesn't seem
to vary very significantly.
Many authors have considered
that host susceptibility factors account more for dandruff than the lipase
activity of the microbe. Although there is sufficient evidence on the growth
promotion role of various lipids on Malassezia,
a clear-cut correlation on the quantitative or qualitative profile of lipids in
the infected and control subjects is lacking.[31] An in
vitro study using Tween 80, a water soluble ester of low chain (C17) fatty
acids, which can serve as substrate both for lipase and esterase reveal that
growth inhibition was observed with the addition of esterase inhibitors such as
di-isopropyl fluorophosphates or quinine while the
lipase inhibitors sodium fluoride seldom affects the growth. Studies on the
growth supporting ability of various water-soluble triglycerides such as glyceryl esters of long chain fatty acids triolein (C17) and short chain tributyrin
(C4) showed that long chain fatty acids have growth-supporting ability.[31]
Dandruff
and hair:
The severity of dandruff ranges from to severe among
subjects, possibly the scales may be trapped in the mesh of crowded terminal
hair prohibiting them from being lost. This dandruff-hair relationship may, in
part, explain the absence of dandruff in bald pates and hairless or shaved
sites and in regions of vellus hairs. The presence of
dandruff may precede or accompany telogen effluvium.[32]
It may also exacerbate androgenetic alopecia. On a
two-day survey, it has been observed that about 100-300 numbers of hairs were
shed in dandruff sufferers instead of 50 – 100 in normal subjects.[10]
In some cases of dandruff, hair shedding may be a
result of alterations in the teloptosis process (exogen phase) and hair eclipse phenomenon. Interestingly,
some of the antidandruff compounds, especially ketoconazole, may limit the
progression of androgenic alopecia.[32,33,34]
ABO blood groups and dandruff:
Another interesting study linking the role of ABO blood
group carriage rate of dandruff reveals that ABO blood group system does not play a
role either in the prevalence or chronicity of
dandruff.[35] The role of ABO
blood group in certain other fungal skin diseases is well established. The
cross reactivity between the fungal cell wall protein and the isoantign of ABO blood groups is presumed to be the cause
for the selective susceptibility of certain blood group subjects to fungal
diseases. [36]
Changing
perspectives:
Many attempts have been made
to understand the pathogenesis and pathogenecity of dandruff. De Angelis et al[37] ,give an interesting
result - that M. restricta and M. globosa
are the most prevalent in dandruff affected population than M. furfur. They have also shown, concomitant with the
elimination of these organisms, the remission of dandruff symptoms in all the
cases they have studied. They hypothesized that species' specificity and
specific targeting is required to combat dandruff. However, an earlier study of
Faergemann in 2002[38] showed the presence
of M. restricta to a very less extent in
dandruff affected population.
A further twist in the understanding of the role of M.restricta in dandruff came
with studies of Sugita et al.[39]
The genotype analysis of M. restricta revealed that only a specific genotype of
the organism plays a significant role in atopic dermatitis and dandruff
although the prevalence of the organism is universal. Despite the elusive and
idiopathic nature of dandruff, it remains a problem for great commercial
exploitation.
Treatment of Dandruff:
Therapy of dandruff may include three different basic
principles
1. Principles of Dandruff
Treatment:
(i)
Symptomatic Treatment:
·
Reduction
of itching (pruritus)
·
Reduction
of scale formation (desquamation) Symptomatic treatment is often achieved by
frequent hair washing with normal shampoo that does not contain any active
ingredients. The effect is due to the surfactants in the shampoo but is usually
only transient.
(ii) Causal Treatment:
·
Reduction
of Malassezia yeast
·
Reduction
of inflammation of the scalp
·
Reduction
of proliferation of skin cells
Causal treatment includes the repeated use of anti-squamolytic agents and anti-fungal agents. Anti-squamolytic agents include salicylic acid and coal tar
which both reduce skin proliferation and promote desquamation. The most
frequent antifungal agents are tea tree oil, piroctone
olamine, zinc pyrithione,
selenium disulphide, terbafine, and ketoconazole. All
are active against yeast and reduce inflammation of the scalp.
(iii) Prevention of Relapse:
Prevention of regrowth of Malassezia yeast Regrowth of
yeast on the scalp can be avoided by using of anti-fungal shampoos at regular
intervals (e.g. 1-2 times a month).
Depending on the active agent used and the frequency of
hair shampooing the success rate of these treatments are usually high. Frequent
cleaning of the scalp with a standard shampoo containing just surfactants but
no active ingredients is often sufficient to control minimal dandruff. In fact,
the surfactants in hair shampoos are themselves therapeutic agents since they
detach the superficial horny skin cells including the microorganisms inhabiting
them. Surfactants can therefore be regarded as dispersing agents for fine
dandruff. However, although surfactants provide immediate results, the effect
remains weak to moderate and is only transient. This effect of surfactants can
further be increased by using ‘harsher’ shampoos (change from a ‘mild’ to a
‘normal’ hair shampoo) which are able to eliminate dandruff almost completely.
However, shampoos with harsher surfactants are more irritant resulting in a contrary
effect since they promote inflammation of the skin. A vicious circle is then
established. The addition of squamolytic agents such
as salicylic acid or tar derivatives have been advocated and used very
successfully. Coal tar is most frequently being used. As an added bonus, coal
tar has a natural conditioning effect, which adds softness and shine without
adding the oils contained in conditioning products. A vital stage in dandruff
treatment was reached with the use of antifungal agents including zinc pyrithione, piroctone olamine, selenium disulphide, terbafine,
and ketoconazole. Ketoconazole has demonstrated its superiority in terms of
antifungal activity against Malassezia. It has been
shown that tea tree oil is active against a wide range of microorganisms
including Malassezia and thus may also be effective
in dandruff. In fact, a study has shown that the use of a 5% tea tree oil
shampoo resulted in a 41% improvement in the dandruff severity core compared
with 11% in the placebo group. Significant improvements were also found in the
itchiness and greasiness.[23]
Chemo-Antidandruff agents:
Antifungal drugs (such as ketoconazole) are often found
in anti-dandruff shampoos. The antifungal drugs inhibit the yeast Malassezia globosa which encourages seborrhoeic
dermatitis and tinea versicolor.
1.Classification
of Antidandruff Agent:
1) Salicylic acid
2) Sulphur
3) Zinc pyrithione
4) Selenium sulphide
5) Coal tar
6) Steroid
a. Eg: Clobetasol
propionate
7) Imidazole Antidandruff agent
a. Eg: Ketoconazole, Fluconazole,
Climbazole, Econazole, Metronidazole
8) Hydroxypyridones
a. Eg: Ciclopirox olamine, Piroctone Olamine
9) Povidone iodine
(i) Salicylic
Acid:
Salicylic acid is a beta-hydroxy
acid keratolytic agent that is useful in removing
scaly, hyperkeratotic skin; it decreases cellto- cell adhesion between corneocytes.
Although the mechanism of action of organic acids is unclear, it may involve
the release of desmogleins and the disintegration of desmosomes. Activation of an endogenous pathway,
responsible for normal cell separation, may also be involved, but this
hypothesis has not been confirmed.[40]
Keratolytic
Effect of salicylic Acid:
One of the major properties of salicylic acid is its
ability to remove skin cells of the most upper layer of the skin, the stratum corneum. This keratolytic effect
is dependent on the concentration of salicylic acid used in a cream. For
example, at a concentration of 10 - 15% salicylic acid shows a keratolytic effect already after 2 or 3 days. At 5% and 1%
desquamation of skin cells is seen after 7 and 10 days, respectively. Hence,
salicylic acid is widely used as major ingredient for peelings or other exfoliant or abrasive skin treatments. Such peeling
products contain salicylic acid usually at concentrations between 0.5 - 3%.
Whereas the upper limit of 20% of is applied only in dermatological
(prescription) products, the use of salicylic acid at this level has also been
recommended for face masks. For anti-warts products salicylic acid is usually
used between 12 - 40%. Besides removing old cells and horny debris from the
skin, keratolysis has also the advantage that it
facilitates the penetration of other active ingredients into the skin.
Salicylic acid is therefore often added to skin care products that contain
active ingredients in order to increase their absorption and efficacy.it still shows significant effects and is
therefore widely used in anti-inflammatory creams and ointments.[41]
It can also be prepared by the hydrolysis of Aspirin
(acetylsalicylic acid) or methyl
salicylate (Oil of Wintergreen) with a strong acid or
base.[42]
Structure:
(ii) Sulphur:
Sulfur is a yellow, nonmetallic element with both keratolytic and antimicrobial properties. The keratolytic effect is thought to be mediated by the
reaction between the sulfur and the cysteine in keratinocytes, whereas the antimicrobial effect may depend
on the conversion of sulfur to pentathionic acid by
normal skin flora or keratinocytes.[43,44]
The keratolytic properties may promote fungal
shedding from the stratum corneum.[45] The
precise mechanism of action is still unknown.[46] Leyden et al.
studied the combination of 2% sulfur and 2% salicylic acid in a shampoo base
(e.g., Sebulex, Westwood Squibb) in a double-blind,
controlled trial using both clinical assessment of scaling and corneocyte counts.[47] They observed
significantly greater and earlier reductions in both the degree of scaling and
in corneocyte counts in subjects using the 2%
sulfur/2% salicylic acid combination than in those using either the active ingredient
alone or the shampoo vehicle.
Sulfur in the solid state ordinarily exists
as cyclic crown-shaped S8 molecules. Sulfur is corrosive to many
metals via the process called tarnishing.[48]
(iii) Zinc:
It is thought that zinc pyrithione
(ZPT) heals the scalp by normalizing epithelial keratinization,
sebum production, or both. Some studies have also shown a significant reduction
in the numbers of yeast organisms after the application of zinc pyrithione.[49,50] A study by Warner et al.
demonstrated a dramatic reduction of the structural abnormalities found in
dandruff with the use of zinc pyrithione shampoo[51]
the number of Malassezia organisms
decreased, parakeratosis was eliminated, and corneocyte lipid inclusions were diminished. Therefore,
normalization of the stratum corneum ultrastructure by zinc pyrithione
is thought to be secondary to the correction of the pathology in the living
epidermal layers.
Its antifungal effect is proposed to derive
from its ability to disrupt membrane transport by blocking the proton pump
energizes the transport mechanism. Experiments have suggested that fungi are
capable of inactivating pyrithione in low
concentrations[52]
Structure:
Marketed preparation:
DANTUFF-Z-48%
(iv) Selenium Sulphide:
It is thought that selenium sulphide
controls dandruff via its anti-Pityrosporum
effect rather than by its anti-proliferative effect;[53]however,
it also significantly reduces the rate of cell turnover. It has anti-seborrheic properties and appears to produce a cytostatic effect on cells of the epidermis and follicular
epithelium. Selenium sulphide is available over the
counter as a 1% shampoo and by prescription only as 2.25% (Selseb,
Doak Dermatologics) and
2.5% shampoos. A study by Danby et al. compared ketoconazole 2% shampoo (e.g., Nizoral, McNeil Consumer)with selenium sulphide
2.5% shampoo (e.g., Selsun) in 246 patients with
moderate-to-severe dandruff in a randomized, double-blind, placebo-controlled
trial.[54] Both ketoconazole and selenium sulphide
were effective in treating dandruff, but ketoconazole was better tolerated
because of its fewer adverse drug effects (ADEs). Excessive oiliness of the
scalp is a significant ADE for many patients who regularly use selenium sulphide to control dandruff. Pierard-Franchimont
and Pierard studied the sebum excretion rate in 52
men using anti-dandruff treatments.[55] At the end of the five-week
treatment period, the rates of sebum excretion showed an average increase of
58% with the use of selenium sulphide, an increase of
3% with ketoconazole, and an increase of
5% with econazole (e.g., Spectazole,
OrthoNeutrogena). Rapaport
compared the anti-dandruff efficacy of four shampoos in 199 patients: selenium sulphide 1% (Selsun Blue, Chattem, Inc.), zinc pyrithione
1% (Head and Shoulders, Procter and Gamble) coal tar extract 5% (Tegrin, GlaxoSmithKline), and a shampoo vehicle (Flex,
Revlon).[56] Subjects using Selsun Blue
experienced significantly greater improvement of symptoms than did any of the
other groups. Van Cutsem et al. compared the in
vitro antifungal activity of ketoconazole 2%, selenium sulphide
2.5%, and zinc pyrithione 1% and 2% against M. furfur in guinea pigs.[57] Ketoconazole was
found to be the most effective for reducing M. fufur
counts, but results with selenium sulphide and 1%
and 2% zinc pyrithione were comparable. The
anti-dandruff effects of ketoconazole were superior to those of selenium sulphide and zinc pyrithione.[57,58]
Selseb (Doak) is a
prescription-only combination of selenium sulphide 2.25%
in a urea vehicle with zinc pyrithione.
Uses: Selenium sulfide is used as an ingredient in
antidandruff shampoos and as a constituent of fungicides (ATSDR 1996).
Prescription strength and nonprescription strength medications contain 2.5% and
1% selenium sulfide, respectively (MEDLINEplus 2001).
Approximately 440 lb of selenium sulfide were consumed for pharmaceutical and
cosmetic products in the early 1970s (IARC 1975).[59]
Structure:
(v) Tar:
Although tars have been classically used to treat psoriasis,
they offer an effective therapy option in treating dandruff as well. Problems
with staining, odour, and messiness in its
application make tar a second-line therapy for most patients. Tar gels contain
coal tar extract, and they are generally less messy and smelly than tar itself.
Tar shampoos work through antiproliferative
and cytostatic effects, although definitive analyses
are difficult because of the large number of biologically active components in
coal tar products. Tar products disperse scales, which may reduce Malassezia colonization.[60] In
the mouse model, topical application of tar suppresses epidermal DNA synthesis.
pierard-Franchimont et al. conducted a randomized, doubleblind study to compare two groups of 30 volunteers
with moderate- to-marked dandruff using either a non-tar shampoo (2% salicylic
acid, 0.75% piroctone olamine,
and 0.5% elubiol) or 0.5% coal tar shampoo.[61]They
observed a significantly greater reduction of Malassezia
species counts in the non-tar group; however, subjects in both groups
experienced clinical improvement.
(vi) Steroids:
The pharmacokinetic properties of topical
corticosteroids depend on the structure of the agent, the vehicle, and the skin
onto which it is applied. Topical corticosteroids work via their anti-inflammatory
and antiproliferative effects. On the scalp, lotions
or solutions having moderate-to-high potency are typically used. Clobetasol propionate 0.05% (Clobex,
GlaxoSmithKline) is available in a shampoo form. Although no studies currently
exist regarding the efficacy of steroid shampoos in managing dandruff, the
efficacy of topical steroid applications has long proved effective in treating
the condition.[62] Topical steroids are often used in combination
with other dandruff treatments such as antifungal agents.
Structure:
(vii) Imidazole
Antifungal Agents:
Imidazole topical antifungals such as
ketoconazole act by blocking the biosynthesis of ergosterol,
the primary sterol derivative of the fungal cell membrane. Changes in membranepermeability caused by ergosterol
depletion are incompatible with fungal growth and survival. Ketoconazole is a
broad-spectrum antimycotic agent that is active
against both Candida albicans and M. furfur. Of all of the imidazoles
currently available, ketoconazole has become a leading contender among
treatment options because of its effectiveness in treating seborrheic
dermatitis. A ketoconazole 1% shampoo has been approved for over-the-counter
use, and a 2% shampoo is available by prescription (Nizoral).
Rare ADEs include irritation and stinging. Ketoconazole 2% shampoo has been
studied extensively in more than 2,000 patients with dandruff or seborrheic dermatitis. Compared with placebo, the shampoo
has been consistently more effective. In a randomized study comparing the efficacy
of a four-week trial of ketoconazole 2% shampoo with zinc pyrithione
1% shampoo, Pierard-Franchimont et al. found
ketoconazole to be statistically significantly superior (with subjects showing
a 73% improvement) the other (a 67% improvement). [63]
As an antifungal, ketoconazole is structurally similar
to imidazole and interferes with the fungal synthesis of ergosterol, a constituent of fungal cell
membranes, as well as certain enzymes. As
with all azole antifungal agents, ketoconazole works
principally by inhibiting the enzyme cytochrome P450
14-alpha-demethylase (P45014DM). This enzyme participates in the sterol biosynthesis
pathway that leads from lanosterol to ergosterol.
Lower doses of fluconazole,climbazole and itraconazole are required to kill fungi compared to
ketoconazole, as they have been found to have a greater affinity for fungal
cell membranes.[64]
Structure
Ketoconazole:
Marketed preparation: DANTUFF-
Fluconazole:
Like other imidazole- and triazole-class
antifungals, fluconazole
inhibits the fungal cytochrome P450
enzyme 14α-demethylase. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase.
This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane,
and subsequent accumulation of 14α-methyl sterols. Fluconazole
is primarily fungistatic,
however may be fungicidal against certain organisms in a dose-dependent
manner. It is interesting to note that, when fluconazole
was in development at Pfizer, it was decided early in the process to avoid
producing any chiral centers in
the drug so that subsequent synthesis and purification would not encounter
difficulties with enantiomer separation and
associated variations in biological effect.
A number of related compounds were found to be
extremely potent teratogens, and were subsequently
discarded.[64]
Fluconazole:
Climbazole:
Climbazole is a topical antifungal chemical commonly used in the treatment of human fungal skin infections like dandruff and eczema. Its chemical structure and properties are similar to other fungicides like ketoconazole and miconazole
. It is most commonly found as an active ingredient in OTC anti-dandruff and anti-fungal products, including shampoos, lotions and conditioners. It may be accompanied by other active ingredients like zinc pyrithione or triclosanStructure: ciclopirox olamine:
1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-(1H)pyridinone,2-aminoethanol
salt
Tonics, Dressings andother hair
grooming aids.
(5)
Gupta AK, bluhrn R: Seborrheic Dermatits. JEADV 2004, 18: 13-26.
(20)
Pierard GE, Pierard FC. Squamometry in acute
photo damage. Skin Res Technol 1995;1:137-9.
(22)
instoresnow.walmart.com/.../01_CHA_10109_0500_SelsunBlue_D_dandruff_US_ENG_01.pdf
(38)
Faergemann J. Atopic
dermatitis and fungi. Clin Microbiol
Rev 2002;15:545-63.
(42)
http://en.wikipedia.org/wiki/Salicylic_acid
(43)
Shapiro J, Maddin S.
Medicated shampoos. Clin Dermatol 1996; 14:123–128.
(45)
Lin AN, Reimer RJ, Carter DM. Sulfur revisited. J
Am Acad Dermatol 1988;18:553–558.
(46)
Gupta AK, Nicol K. The use
of sulfur in dermatology. J Drugs Dermatol 2004;3(4):427–431.
(48)
http://en.wikipedia.org/wiki/Sulfur.
(52)
http://en.wikipedia.org/wiki/Zinc_pyrithione
(59)
ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s160sele.pdf
(68)
www.specchemind.com/images/po.pd
(69)
www.makingcosmetics.com/inci-list/inci-anti-dandruff.htm
Received on 10.02.2011
Accepted on 20.02.2011