Jose 2018

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Accepted: 2 January 2018

DOI: 10.1111/jocd.12504

REVIEW ARTICLE

Role of solid lipid nanoparticles as photoprotective agents in


cosmetics

Jobin Jose MBA, MPharm, PhD | Gladyston Netto MPharm

Department of Pharmaceutics, N.G.S.M.


Institute of Pharmaceutical Sciences, Nitte Summary
University, Mangalore, India Background: Novel drug delivery systems have gained popularity since last two
Correspondence decades because of its advantages over conventional dosage forms. Effect of UV
Jobin Jose, Department of Pharmaceutics, radiation on skin can cause either acute or chronic damage to our skin. Solid lipid
N.G.S.M. Institute of Pharmaceutical
Sciences, Mangalore, India. nanoparticles (SLNs) were developed as novel carrier over the conventional carrier
Email: jjmattam07@gmail.com systems like liposomes and emulsions. The SLNs were selected as a carrier for the
formulation because of its ability to protect the labile drug particles, the ability to
make the drug release in a controlled manner, and occlusive property of the SLNs.
Objective: The current review is an attempt to focus on the characteristics of solid
lipid nanoparticles, methods for the preparations, and their cosmetic applications
along with some future perspectives of the nanodrug delivery systems.
Methods: A review of the current literature of solid lipid nanoparticles (SLNs) as
novel carrier showed better photoprotection in sunscreens.
Results and conclusions: The disadvantages of conventional sunscreens can be
overcome by incorporation of solid lipid nanoparticles. On comparing the lipid nano-
based systems with traditional cosmetic products, the occlusion can be achieved
without the use of paraffin and other greasy oils. The film formed by lipid nanopar-
ticles will be smooth as compared to the inflexible films formed by the paraffin.
Newer approaches may lead to even better results. They also possess excellent UV-
blocking activity and showed better photoprotection.

KEYWORDS
photoprotection, solid lipid nanoparticles, sunscreens, UV radiation

1 | INTRODUCTION causes wrinkles, skin burns, and an increased risk of developing


skin cancers.2
Sunshine is good for our skin which provides necessary vitamins UV light reaching to earth is classified into UV A, UV B, and UV
for our body; increase in release of hormones such as serotonin C radiations based on the difference in wavelengths3 (shown in
makes the person feels more focused and calm.1 Getting exposed Table 1). UV A rays can lead to the aging of skin and even cause
to sunlight is also a better treatment for nonseasonal depression. harmful effects to the elastic and collagen fibers of the skin. Expo-
Besides these advantages, there are several disadvantages for the sure to UV B rays is having more risk than UV A because this can
exposure to sunlight. Excessive exposure to the UV light can cause sunburn or erythema, and it also intensifies the photoaging
cause many health problems such as aging of skin and photoder- effect.4 UV C rays are mostly filtered by the atmospheric layer
2
matoses. The exposure to sunlight may alter our DNA, and it before it reaches the earth. Ozone layer does not have the ability
damages connective tissues and collagen. This leads to hyperpig- for the complete absorption of UV B light.5 UV A rays penetrate
mentation and loss of skin elasticity. Overexposure to UV rays through the skin layers like epidermis and dermis and aggravate the

J Cosmet Dermatol. 2018;1–7. wileyonlinelibrary.com/journal/jocd © 2018 Wiley Periodicals, Inc. | 1


2 | JOSE AND NETTO

T A B L E 1 Types of UV radiation for a longtime can cause sunburn that even can lead to non-
Types of UV radiation Wavelength range (nm) melanoma skin cancer.12

UV A 320-400
UV B 290-320
3 | PENETRATION OF UV RADIATION
UV C 200-290

The harmful rays UV C rays will be absorbed by the ozone layer as


early aging of skin. One of the major causes of skin cancer is UV well as the other layers of gases in the atmosphere. Due to the
radiation because of these facts the sunscreen products are gaining increase in the pollutants, the percentage of depletion of the ozone
more importance. Sunscreen formulations are available in various layer is increasing day by day; as a result, the exposure to the UV
forms like shampoo, cream, and lotions.6 rays will be more.12 When 1% of the ozone layer depletes, about
The current market is flooded with more sunscreen formula- 30 000 death where reported in North America in a year.13 If the
tions because of the increase in demand of the photoprotective ozone layer depletion continues, then the death rate will be
agents for customers. Currently available sunscreen formulations increased by 1%-10%.
mainly contain chemicals or synthetic UV filters.7 A modern UV fil- The percentage of the UV B rays reaching the earth surface is
8
ter is the active ingredient in sunscreens, and it should be nontox- less in percentage but when it comes in contact with skin, the
ic, water resistant, photostable, and easy to formulate. The lowest chance of causing skin cancer as well as sunburn is very high. Sun-
possible percutaneous permeation of UV filter should occur to burn is causing after 12-24 hours of exposure.14 Many studies
9
ensure the safety and efficacy. The percutaneous permeation of reported that UV B rays are harmful than UV A rays, but recent
UV filter depends on various physicochemical properties, and all studies showed that UV A rays also cause harmful effects because it
the formulated sunscreens must undergo strict efficacy and safety penetrates to the deeper layers of the skin and this cause damage to
studies.10,11 Recently, the UV protective effects of herbal deriva- the elastin fibers and blood vessels.
tives have been investigated, and now, the scientists are focussing
mainly on herbal formulations.12 Herbs such as carrot seed, almond
oil, soya oil, and green tea were having a good photoprotective 4 | BIOLOGICAL EFFECTS OF UV
activity. Based on the studies carried out, the researchers stated RADIATION
that the herbs possess more action than synthetic products. The
herbal formulation absorbs into deeper layers of skin and provides When skin is exposed to UV rays, the synthesis of vitamin D occurs
better action at lesser concentration. Natural polyphenols have the which is essential for the healthy bones. Oversynthesis of vitamin D
ability to absorb the UV radiation.13 The topical application of the is also harmful for the skin, but this is barred by the pigmentation
formulation will prevent the penetration of UV light into the dee- and keratinization mechanism.11 When skin is exposed to the UV,
per layer of the skin. Polyphenols mainly absorb UV B rays and a tanning reaction occurs. The tanning reaction can be classified into
part of UV A rays. The use of polyphenols is beneficial in avoiding two, that is, immediate tanning and delayed tanning. The immediate
the sunburn, prevents DNA damage, and it also acts as antioxi- tanning caused within one hour of exposure to the sunlight and will
dant.14 be cured after 3 hours and the delayed tanning caused after 2-
Solid lipid nanoparticles (SLNs) are colloidal carriers which are 3 days of exposure to sunlight. Delayed tanning will be cured after
developed as an alternative for the traditional carriers. SLNs gain 9-12 months. In this, the production of new melanin cells will occur,
more importance because of its uniform size, lesser surface area, and and subsequent migrations of these cells to the surface of skin will
the high drug-loading capacity. The application of SLN in the field of occur.12 The synthesized melanin cells will protect the skin from UV
topical formulations improves the therapeutic efficacy by maintaining damage, and this melanin will also act as a free radical scavenger.
a controlled drug release pattern and protects the drug having less The keratinization is a natural defensive mechanism to prevent pene-
stability. SLNs can be used in both organic and inorganic sunscreen tration of the ultraviolet rays to deeper skin layers. Skin cancer, ery-
formulations.15 thema, or sunburn are caused due to the exposure to the sunlight
for a particular period of time, and as per the reports of the studies
conducted, skin cancer is the second most common cancer in United
2 | RADIATION AND NEED FOR States.14 UV radiations are intended to exert many of their adverse
PROTECTION biological effects due to the liberation of reactive oxygen species as
a result of photosensitization and photochemical reactions.15 The
Light is an essential parameter for the life on earth. The UV light human skin has a natural defense mechanism to act against the
varies in the range of 100-400 nm. On the basis of the wavelength harmful effects from UV radiations. Antioxidants are capable to inhi-
of light, we can divide it into three: UV A, UV B, and UV C.6 bit lipid peroxidation induced by UV radiations. They are found to
The sunrays that cause sunburn usually come from the shorter be scavenging the reactive oxygen species and reduce chronic cuta-
wavelength end of the sunlight spectrum. Exposure to the UV rays neous damage.16 Moreover, the human sweat protects the skin from
JOSE AND NETTO | 3

erythema, induced by UV radiations due to its partial opacity to UV a thickness of 2 mg/cm2. Sunscreen having a SPF of 15 means it gives
17
radiations. The film of sweat is capable of absorbing UV light. 93% protection from UV rays.29 The percentage of protection can be
improved by increasing the SPF value, that is, a formulation having SPF
value 30 + will give a protection of 98%. The higher number of Sun
5 | SUNSCREEN FORMULATIONS Protection Factor blocks more of the sun’s UV rays. But in reality no
sunscreen can block 100% of the UV rays. The peoples who have fair
The productions of sunscreens were developed due to the increase in skin are more prone to sunburn; they should use the sunscreen having
injurious consequences of UV radiation on human skin. Sunscreens a SPF of 30 + . If chance of causing tanning is high, then it is better to
can be classified into two: physical sunscreens (inorganic filters) and choose a broad spectrum sunscreen which has a SPF value ranging from
chemical sunscreens (organic filters). They are composed of inert 8 to 15. Those who have dark pigmented skin are less prone to sun-
molecules which have the ability to reflect the UV rays. The most com- burn.30 Sunscreen creams and ointments are more preferred for the one
mon ingredients used in physical sunscreens are the fine particles of who has dry skin. Those who have oily skin are better to choose sun-
titanium dioxide of particle size ranging from 20 to 30 mm.18 Due to screen having a lighter base such as lotion or gel.31
the presence of inert particles, there is a less chance of breakdown of The ideal properties of sunscreens include:
particles; irritation to the skin can be avoided. Due to the small size of
the particles, percentage of absorption of particles through the skin is • Sunscreens should absorb the UV rays in the range of 2900 to
less, as well as it will provide protection against the UV B and UV A 3300 
A, because getting exposed to these types of rays increases
rays.19 The mechanism of physical sunscreens is that they reflect and the chance of causing sunburn.32
scatter the UV light and thereby prevent the absorption of UV light • It should be compatible with the environmental conditions.33
into the skin. The examples of physical sunscreens are zinc oxide and • Even though the product undergoes deterioration, the decom-
titanium dioxide. The efficiency of the physical sunscreens mainly posed products should be nontoxic and nonirritating.34
depends on the film thickness, refractive index, and particle size of the • The formulation should possess neutral pH; thus, it will not cause
sunscreen formulation.20 The chemical sunscreen absorbs the UV light, any effects on skin.35
and they disperse the energy into different ways. Once the organic fil- • The water solubility of the formulation should be less, to avoid
ters absorb incident radiation, they are excited to higher energy levels the loss of formulation during perspiration.36
by absorbing a photon of energy. As the excited state is not stable, it • It should be nonvolatile in nature.
emits the excess energy and returns back to the ground state (stable • Rapid absorption of sunscreen through the skin is not preferred.
state). To achieve this transition, there are two possibilities, that is, the
release of energy occurs at a longer wavelength than the incident radi-
ation (as fluorescence) or by release of heat. These transitions can be 7 | GENERAL PROCEDURE FOR THE
repeated numerous times process called resonance.21 The photopro- PREPARATION OF SUNSCREEN
tection activity of a sunscreen is governed by the Sun Protection Fac-
tor (SPF)22. The important parameters such as chemo blocking activity The method will also vary based on the type of formulation. If the
and photoprotective action determine the ability of the sunscreen.23 formulation is solution type or aqueous, then it is prepared by dissolv-
The chemical sunscreens are composed of synthetic components such ing the active ingredients along with the excipients in the vehicle.37
as octocrylene. They absorb the UV radiation in an effective manner Sunscreen creams and emulsions are prepared by heating the
and possess protection factor in range of 4-30. The vehicles can also lipid phase and aqueous phase separately and mix together by stir-
affect skin penetration/permeation of sunscreens. Chatelain et al ring. During stirring, add the active ingredients to the cream and mix
compared the skin penetration of UV filters from two vehicles, that is, uniformly in one direction.38
petrolatum jelly and gel. They concluded that the usage of right vehicle Gel type and high viscous aqueous preparations are prepared by
significantly reduces the risk associated with the skin penetration of dissolving the thickening agent and the other ingredients including
UV filters.24 The composition of vehicle also affects the in vitro skin active molecule in two separate beakers, and then, the dispersion of
permeation and in vitro release of most commonly used UV filter thickening agent is mixed with the ingredients in second beaker and
octylmethoxycinnamte.25,26 The added viscosity enhancing agents also stir well to form gel.39
play major role in penetration of a sunscreen.27,28

8 | THE CHARACTERISTICS OF SOLID


6 | SUN PROTECTION FACTOR (SPF) LIPID NANOPARTICLES

Sun Protection Factor (SPF) is determined by comparing the duration of The formulation of a cosmetic preparation is not only concerned
time needed to produce the sunburn on sunscreen-protected skin to about the elegance of the product, but also on the appearance of
the duration of time needed to cause sunburn on exposed skin. It the product.40 The SLNs play a vital role in the field of cosmetics
describes the protection provided by sunscreen when applied on skin at because of their size range and morphology.41
4 | JOSE AND NETTO

9 | OCCLUSION, ADHESIVENESS, AND consideration because change in isotonicity can cause irritation to
SKIN HYDRATION skin.50

The occlusive nature of solid lipid nanoparticles is due to the formation


of monolayer film over the surface of skin; theoretically, the monolayer 13 | METHODS FOR THE PREPARATION
is formed when 4 mg of formulation of size about 200 nm, when OF SOLID LIPID NANOPARTICLES
applied on an area of 1 cm2.42 The in vitro testing for the occlusive
property of the SLN was determined by de Vinger. The evaporation of The different methods used for the preparation of solid lipid
water molecules depends on the particle size. When particle size nanoparticles are as follows:
decreases, the rate of evaporation of water molecules also reduces
because the surface area of the particles increases correspondingly. • Hot homogenization method
The application of formulation containing SLN on dry horny layer of
the skin is good because when lipid nanoparticles applied to the skin, a This method is usually applied for the lipophilic drugs as well
fusion occurs and leads to the formation of a dense film.43 as for the insoluble drugs. In this method, the drug is dissolved in
the melted lipid, and the melted lipid containing drug is stirred
along with the hot surfactant solution of temperature and will be
10 | UV-BLOCKING EFFECT 5 or 10°C more than the temperature of the lipid. The obtained
pre-emulsion will be passed through high-pressure homogenizer,
Nowadays solid lipid nanoparticles are used as novel carriers in sun- and the cycles applied for this processes are 500 bar or two
screens due to its UV-blocking ability. The solid lipid nanoparticles have cycles at 800 bars. This method is not applicable for the water-
the ability of scattering and reflecting the UV radiations. A synergistic soluble drugs because the drug entrapment efficiency will be
photoprotective power will be obtained after incorporation of sun- reduced.51
44
screens into SLN, and they can act as physical sunscreens. Better pho-
toprotection can be achieved by combination of solid lipid nanoparticles
45
• Cold homogenization method
with molecular sunscreens. Sunscreens were incorporated into solid
lipid nanoparticles that showed better UV protection by enhancement of This method is particularly preferred for the hydrophilic drugs. In
SPF.46,47 Modern sunscreens contain nanoparticles, which scatter or this method, the pre-emulsion obtained by crushing and dissolving
reflect UV radiations more efficiently than conventional sunscreens.48 the lipid containing drug mixture and added to the cold surfactant
solution and homogenized for 5-10 cycles at 1500 bar pressure.52,53

11 | SMOOTHNESS, LUBRICATION, AND • Microemulsification solidification method


EMOLLIENCY
In this method, the lipid phase is usually oil, loaded with drug
Cosmetics need appreciable lubricant property especially if they are kept at 65-75°C, and this mixture will be dispersed in aqueous phase
intended to be applied on skin. The lipid nanoparticles possess at cold temperature about 2-3°C under mechanical stirring, and
spherical shape, and they exhibit excellent lubrication action. The washing of the obtained dispersion will be carried out. After freeze-
lubricant property can be evaluated by rheological studies. The solid drying of the washed dispersion, the particle size of the resultant
lipid nanoparticles containing formulations are particularly useful in mixture is about 100 nm.54
skin irritation and allergic reactions due to its excellent lubricant
action. The emolliency of the formulation depends on the type of • Supercritical fluid method
lipids and surfactants used in the preparation.49 The lipids such as
tripalmitin and tristearin will produce highly crystalline particles, and In this method, the supercritical fluid such as carbon dioxide was
they also possess high occlusive property. used for the development of solid lipid nanoparticles.55 The advan-
tage of this method is that the amount of solvent used in the pro-
cess can be reduced. For this, carbon dioxide (99.99%) is the better
12 | OSMOTIC EFFECTS AND CONTROL choice for this process.56,57
OF PH
• Spray drying method
Care should be taken while formulating cosmetics because if the for-
mulation becomes strongly acidic or alkaline, then it may lead to This method is used as an alternative method for the lyophiliza-
deleterious effects. The advantage of solid lipid nanoparticles is that tion method. When compared to lyophilization method, this method
they can be formulated in the optimal pH range. During the prepara- is quite economical. The drawback of this method is that due to the
tion of topical formulation, the osmotic effects to be taken into excessive temperature and high shear force, it leads to partial
JOSE AND NETTO | 5

melting of the sample and aggregation of the particles may occur. developed by Bose et al it showed better anti-radical activity, better
For spray drying method, the lipid having melting point greater than photoprotection, and good physical stability.65 The in vitro release
70°C is preferred.58 study showed initial burst release of quercetin followed by a pro-
longed release, and thereby, it delays the ultraviolet radiation-
• Solvent injection method mediated cell damage. Gokce et al used the solid lipid nanoparticles
as the carrier for the drug resveratrol for developing the sunscreen
In this method, SLNs are obtained by the rapid injection of lipid formulation by high shear homogenization method and various param-
solution (the solvent used here is hydrophilic agents such as ethanol, eters like the particle size, zeta potential, and drug entrapment effi-
methanol, or ethyl acetate) into aqueous phase containing surfac- ciency, and the obtained results were in appreciable range.66 The
59
tant. encapsulation effect of UV molecular absorbers into solid lipid
nanoparticles was carried out by Lacatusu et al and the in vitro evalu-
ation of UV protection had led to high sun protection factor values.
14 | APPLICATION OF SOLID LIPID Lacatusu et al carried out the studies of solid lipid nanoparticles bear-
NANOPARTICLES IN SUNSCREENS ing UV sunscreens, and they evaluated the photostability and sun pro-
tection factor of the prepared formulation.54
Solid lipid nanoparticles-based sunscreens may act as permeation
enhancers; thereby, it improves the penetration as well as the toler-
ance of the active moiety.60 By the use of SLNs, the concentration of 15 | CONCLUSION
the molecular sunscreen can be reduced and thereby minimize the
side effects associated with it. By the use SLNs as a carrier, there are There are several products which come under the lipid nanoparticles
better options for formulating sunscreens having excellent photopro- and which showed the control release pattern of drug through the
tective actions. The drug entrapment efficiency of the formulation skin. The percentage of toxicity shown by solid lipid nanoparticles is
depends on the selection of the lipids, percentage of the loading less, and hence, it can be safely used in the dermatological and cos-
capacity, and also it depends on the compatibility of the active ingre- metic products to achieve the discrete properties. On the other
61
dients with the lipids used for the preparation of nanoparticles. The hand, during the preparation of the cosmetic and dermatologic for-
SLNs are good carrier systems for the drugs like oxybenzone; thereby, mulation, the nature of the epidermal tissue should keep in mind,
the harmful effects such as skin irritation or contact dermatitis can be that is, the formulation needs to be biocompatible with the natural
minimized.62 The carrier-based sunscreen containing organic sun- protective barrier which can be achieved by the use of solid lipid
screen provides better physical and chemical UV protection action. nanoparticles. On comparing the lipid nanobased systems with tradi-
Recently, lipid nanoparticles are used as carriers for the herbals for tional cosmetic products, the occlusion can be achieved without the
developing sunscreen formulations which are having less noxious use of paraffin and other greasy oils. The film formed by lipid
effect as compared to the synthetic agents such as oxybenzone. nanoparticles will be smooth as compared to the inflexible films
Novel herbal sunscreen preparations reduce the toxic effect as well as formed by the paraffin. To improve the bioavailability, various strate-
increase the photoprotection effect. The study related to compounds gies are currently being developed to formulate drug-loaded solid
like polyphenols has gained more importance in this field.63 The prod- lipid nanoparticles in sunscreen formulations. The studies indicated
ucts such as aloe vera, jojoba, olive, almond, green tea, and safranal that the use of solid lipid nanoparticles as a carrier enhanced the
are being used for the development of herbal sunscreen formulations. bioavailability. These results showed that the solid lipid nanoparticles
The molecules used in the sunscreens should possess the properties could be a promising carrier for sunscreens.
that it should not go through the viable epidermis and dermis of the
skin and on the top layers of the skin (ie, the stratum corneum or the
ORCID
horny layer). By the use of novel carriers such as solid lipid nanoparti-
cles, researchers can improve the nature of the drug molecules used Jobin Jose http://orcid.org/0000-0002-2815-5384
in the formulations.64 The solid lipid nanoparticles of green tea devel-
oped by high shear homogenization method showed better photopro-
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