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Received: 24 June 2021    Accepted: 27 August 2021

DOI: 10.1111/jocd.14441

REVIEW ARTICLE

The revolution of cosmeceuticals delivery by using

nanotechnology: A narrative review of advantages and side
effects

Maha N. Abu Hajleh PhD1  | Rana Abu-­Huwaij PhD2  | Ali AL-­Samydai PhD2  |

Lidia Kamal Al-­Halaseh PhD3  | Emad A. Al-­Dujaili PhD4

1
Department of Cosmetic Science,
Pharmacological and Diagnostic Research Abstract
Centre, Faculty of Allied Medical Sciences,
Background: The qualified and paradigm jump in the formulation and production
Al-­Ahliyya Amman University, Amman,
Jordan of cosmeceuticals refer in some way to the great revolution in nanotechnology.
2
Pharmacological and Diagnostic Research Nowadays, the industry of nano-­formulated cosmeceuticals plays a significant and es-
Centre, Faculty of Pharmacy, Al-­Ahliyya
Amman University, Amman, Jordan
sential role in the evolution and growth of the pharmaceutical industries. This review
3
Department of Pharmaceutical manuscript focuses on the use of nanocarriers in delivering the cosmetic agents into
Chemistry, Faculty of pharmacy, Mutah the target area such as skin, hair, and nails.
University, Al-­Karak, Jordan
4 Methods: Many steps were performed in the preparation of this review including
Centre for Cardiovascular Science,
Queen's Medical Research Institute, identification of different classes of nanocarriers for delivery of nanocosmeceuticals,
University of Edinburgh, Scotland, UK
literature survey of relevantstudies regarding the applications of nanotechnology in
Correspondence cosmeceuticals and their toxicological effects.
Maha N. Abu Hajleh, Department of
Cosmetic Science, Pharmacological and Results: When nanoparticles introduced in the cosmetic industry, the quality and the
Diagnostic Research Centre, Faculty elegance of the final products were raised significantly. Sadly, this revolution is ac-
of Allied Medical Sciences, Al-­Ahliyya
Amman University, Zip code (19328), companied by many health hazards as these tiny molecules can penetrate intact skin
Amman, Jordan. barriers and cause undesired effects. Cosmeceuticals with nanotechnology include
Email: mahaabuhajleh@hotmail.com
sunscreens, hair cleansing products, nail products, and agents fighting fine lines.
Conclusions: The expansion and growth of the cosmetic industry and the introduc-
tion of nanotechnology in cosmeceuticals industry necessitates the urgent need for
scientific research investigating their efficacy, safety profile and use.

KEYWORDS
cosmeceuticals, delivery system, nanocarriers, nanocosmeceuticals, nanostructure,
nanotechnology

1  |  I NTRO D U C TI O N structural rearrangement, the physical characteristics of these novel

Nanotechnology is the science and technology applied in biomedical
engineering, dermatology, medicine, and cosmetics for designing,
production, and characterizations of particles and devices at the
1-­4
molecular level range from 1 to 100 nm. As a result of internal
materials change such as the increase in their surface area and there-
fore act in a differently with the targeted biological systems.5-­7 This
change has a pronounced and significant impact on both the formu-
lation and the delivery system of pharmaceutical and cosmeceutical
preparations.8 Many innovative delivery systems are incorporated

Abbreviations: ACIs, active cosmetic ingredients; AuNPs, gold nanoparticles; HNT, halloysite clay nanotubes; LP, liposomes; NCs, nanocosmeceuticals; NE, nanoemulsion; NPs,
nanoparticles; NSs, nanosystems; O/W, oil in water; ROS, reactive oxygen species; SC, stratum corneum; SLNs, solid lipid nanoparticles; TEWL, trans-­epidermal water loss; TiO2,
titanium dioxide; UV, ultraviolet; W/O, water in oil; ZnO, zinc oxide.

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3818    © 2021 Wiley Periodicals LLC wileyonlinelibrary.com/journal/jocd J Cosmet Dermatol. 2021;20:3818–3828.
ABU HAJLEH et al.
in the manufacturing and formulating of cosmeceuticals. These
include liposomes (LP), solid lipid nanoparticles (SLNs), niosomes,
gold nanoparticles, nanoemulsion (NE), and nanosomes. 2 Moreover,
these systems are promising in enhancing and achieving better de-
livery of the active cosmetic ingredients (ACIs) to their targets and
optimize the stability of vitamins, antioxidants, and other natural or
synthetic products mainly unsaturated fatty acids. These delivery
systems could also maximize the carrier's loading capacity of the
drug, prolong the activity, and improve the biocompatibilities of dif-
9,10
ferent ACIs with other excipients.
Cosmeceuticals represent a twining between pharmaceutical
preparations and those products which are specialized in personal
11
care. Both the stability and the efficiency of these cosmeceu-
ticals are superior to the conventional products of cosmetics. The
incorporation of these cosmeceuticals in treating various hair and
skin conditions shows quantifiable efficacy. These conditions range
from minor dermatological problems, as in dry skin and skin pig-
mentation to those more complicated cases such as photoaging
and skin wrinkles.10,12,13Nanocosmeceuticals have clearly defined
the cosmeceuticals that are delivered in nanovehicles or formu-
lated with the technology of nanoparticles. David Baird announces
nanocosmetics as the first marketable brand of this delivery tech-
nology.11 Nanocosmeceuticals (NCs) are used in hair care prepara-
tions, long-­lasting fragrances, and skincare formulations. Various
applications of cosmetics using nanotechnology are demonstrated
9
in Table 1; Figure 1.
NCs have steady growth and reaches their maximum last de-
cade. There are many advantages of using NCs for delivering active
cosmetic agents, including controlling its release, specifying the
target site, and enhancing the hydration by allowing the occlusive
dressing of the hydrating agents that contribute significantly to in-
creasing skin penetration. 2,14 NCs have the advantage of controlling
the release of the actives from their carrier through physically or
chemically interact between the different component and excipients
in different ratios and preparation methods.15,16
Despite their numerous benefits, NCs have many limitations due
to their high reactivity; this could lead to an increased reactive oxygen
species (ROS) production. These produced ROS are the chief respon-
sibility of nucleic acid damage, damage of protein, the inflammation,
and even degradation of the membranes. Increased ROS levels are
referred to oxidative stress, and it is considered to greatly contribute
to several pathological conditions including neurodegenerative dis-
eases, carcinogenesis, and intrinsic or chronological aging. 17,18
2  |  M E TH O DS E M PLOY E D
Many steps were followed in the preparation of this review includ-
ing identification of the different classes of nanocarriers for deliv-
ery of nanocosmeceuticals, literature survey of relevant studies
regarding the applications of nanotechnology in cosmeceuticals, and
toxicological aspects of nanocosmeceuticals. Relevant data were ex-
tracted and evaluated, and this was made possible by using different
|
      3819
search engines such as Google Scholar, Science Direct, and PubMed
through appropriate keywords, such as nanotechnology, nanocarri-
ers, cosmeceuticals, nanocosmeceuticals, and delivery system.
2.1  |  Nanocarriers for delivery of
nanocosmeceuticals
To date, four classes of nanocarriers are in use for delivering NCs
(Figure 2): the lipid-­based nanosystems (NSs), the polymeric-­based
NSs, the metal-­based NSs, and the additional NSs.19
2.2  |  Polymeric-­based nanosystems
2.2.1  |  Polymeric nanoparticles
In using nanoparticles (NPs) technology, both hydrophilic and hydro-
phobic actives could be dispersed or captured in the final matrix.
Either in the form of a nanocapsule or nanosphere form, the ma-
trix diameter is in the range of 200–­300 nm.9 Natural and synthetic
agents apply to this formulation. Recently, using polymeric NPs is in
increasing demand, particularly for skincare products such as age-­
fighting formulations, antiacne, and moisturizing recipes. Cosmetic
agents that intended to be used on nails also benefited from this
technology by controlling both the release of the coloring materials
and the retention time of the non-­polar coloring agents. 20,21
2.2.2  |  Nanofibers
Nanofibers are composed of a porous structure with a high surface
area; its diameter reaches 500 nm. The porous structure of these
nanofibers encourages their use to facilitate the appropriate release
of the drug from its polymeric matrix. Consequently, a decrease in
the required dose and minimal systemic absorption is achieved.9
2.3  |  Lipid-­based nanosystems
The use of lipid-­based systems in nanoscale as dermal carriers of cos-
metic agents shows good biocompatibility and stability of the car-
ried particles. Also, it enhances skin penetration and thus increases
the efficiency of the active ingredients. All these advantages make it
probable for this system to be integrated into new dosage forms. 20
2.3.1  |  Solid lipid NPs and nanostructured
lipid carriers
Both solid NPs and nanostructured lipid carriers are considered
colloidal delivery systems. These systems have numeral properties
relate to cosmetics in general and skincare products in particular.
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3820      ABU HAJLEH et al.

TA B L E 1  Major classes of nanocarriers for delivery of cosmeceuticals

Class of nanocarriers Types of nanocarriers Uses References

9,20,21
Polymeric-­based Polymeric nanoparticles: Age-­fighting formulations, antiacne, and moisturizing recipes.
nanosystems • Nanocapsules,
• Nanospheres,
9
Nanofibers Used as facial masks, skin care, and renewal products.
9,26,27
Lipid-­based • Solid lipid NPs Are incorporated into skin care products such as moisturizing
nanosystems • Nanostructured lipid carriers creams and sunscreens.
2,9,30
Vesicular systems: -­Liposomes and photosomes are incorporated into skin care
• Liposomes products
• Photosomes -­Ultrasomes aid to repair cellular damages, combat wrinkles,
• Ultrasomes sagging skin, and loss of tone and elasticity.
• Niosomes -­Niosomes are presented in different formulations like beauty care
• Transfersomes and hair care cosmetic products
20,23
Nanoemulsions Nanoemulsions are widely used in hair care products
10,13,27
Cubosomes Promising tool for pharmaceutical and cosmetic formulations
34,35
Metal-­based Gold nanoparticles Can be found in different cosmetic products, as toothpastes,
nanosystems creams, soaps, lotions, deodorants. herbal products-­based
formulations, sunscreens, makeup, and hair cosmetics
36
Silver nanoparticles Improve skin firmness and elasticity, delaying aging process and
proteasome inhibitory activity, being integrated in antiaging
creams, lotions, and deodorants
6,9,37
Silica nanoparticles Can be found in toothpastes, makeup products, hair styling,
deodorants, and skin care.
38
Zinc oxide nanoparticles Incorporated in various cosmetic products as UV filters
38
Titanium oxide NPs Incorporated in various cosmetic products as UV filters
2,39
Additional Dendrimers Dendrimers are present in different hair, nail, and skin cosmetics.
nanosystems Fullerenes Used in skin whitening and sunscreen products. 41

42
Nanocrystals Nanocrystals are developed to improve the solubility of cosmetic
products.

physiochemical specifications. 24Accordingly, the cosmeceuticals

F I G U R E 1  Schematic diagram showing the different applications
of nanotechnology in cosmetic formulations and their valuable
cosmetic effects as modified from Morais et al.9
that are either small in size, contain biodegradable lipids, or even
designed for occlusive hydrating systems are widely delivered
through the SLNs technology.13,25 Moreover, this solid lipid system
is biologically biodegradable and provides long-­term stability for
the controlled-­release medications. 26 Perfumes as well have been
employed in SLNs delivery system, to give the advantage of pro-
longed effect fragrance. 27
The formation of NLCs requires a blend of lipids, in both solid
and liquid states; this will aid in trapping the active ingredients. 23
Higher loading efficiency, and the low leakage risk of the lipophilic
matrix during the determined expiry date are the main advantages of
the NLCs delivery system.9,26

2.3.2  |  Vesicular systems

Among these properties, the submicron diameter scale of the col-
loidal carries in a range of 50–­1000 nm. 21-­23 Those ingredients with
water-­soluble or poorly water-­soluble properties are applicable to
be integrated with the lipophilic constituents. 2 So, the strength
of these systems relied on increasing the delivery efficiency
through either the manufacturing techniques or the constituents’
Vesicles in variable physicochemical properties and different effi-
cacy exist in cosmeceuticals. Vesicular structures importance is due
to their ability to improve dermatological therapies. These struc-
tures facilitate the free transportation of the actives through the
layers of the skin.9
ABU HAJLEH et al.
F I G U R E 2  Summary of the four novel types of nanocarriers including their applications in various cosmeceuticals as modified from
Lochhead 2017.19
2.3.3  |  Liposomes
They are biodegradable vesicles composed of a spherical phos-
pholipid bilayer enclosing an aqueous compartment. 26 The most
frequently used lipids in LP preparations are phospholipid (phos-
phatidylcholine), phosphatidylethanolamine, sphingolipids, glycolip-
ids, and sterols. 21,23 Liposomes diameters range from 20 nm up to a
few hundred micrometers. 27 LPs can be categorized as unilamellar
9
or multilamellar vesicles. Both hydrophilic and lipophilic ingredients
could be encapsulated into LPs within the polar and oil-­soluble cavi-
21
ties, respectively.  This makes them a good choice for delivering a
26
wide range of components in a controlled manner.  Moreover, LPs
vesicles have any other features include biocompatibility, safety, and
11
flexibility.
As a result, LPs can easily encapsulate the active moieties, which
explains their use in variable cosmeceuticals.10,27 LPs are industri-
alized to deliver many active ingredients like fragrance botanicals
and vitamins into skin care products and other coloring cosmetics.
Examples of such cosmetics are antiperspirants, deodorants, body
sprays, and lipsticks. Beautifying products, antiwrinkles, sunblocks,
2
moisturizers, and hair care products are also included.
2.3.4  |  Niosomes
Sel-­
assembled biodegradable components of hydrated non-­
ionic
surfactants made up the vesicle bilayer nanostructures of niosomes.
21
The incorporation of cholesterol or other lipids is optional.
Examples of used surfactants include tweens, spans, brjis, alkyl
amides, alkyl ether, and polyoxyethylene. Esters are also among the
used substances like sorbitan ester and crown ester.10,28 Factors
affecting the production of niosomes are surfactants nature, drug
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      3821
structure, membrane compositions, and the hydration temperature.
The vesicle diameters are in the range of 100 nm−2 µm. This system
is applicable to deliver components of a wide range of hydro-­and
lipophilicity. 29Different cosmetic formulations could get benefit from
the use of niosomes as a carrier system. These include beauty, hair,
and skin care products. Ingredients in need to penetrate the stratum
corneum skin layer to modify its lipid structure are encouraged to be
formulated into niosomes; as they have improved skin permeability
effects and could enhance the delivery of the carried agents into the
living tissues.30 In this system, both the stability of the actives and
the bioavailability of the ingredients are enhanced.31 Furthermore,
they have high encapsulation efficiency at a cost-­effective price
compared to LPs.13
2.3.5  |  Nanoemulsions
A biphasic oil-­in-­water system (O/W), water-­in-­oil (W/O) system,
and multiple systems with layers of internal phases (W/O/W and
O/W/O) are all fall in the category of nanoemulsions. These sys-
tems have a droplet diameter of 100–­500 nm. The efficiency of
nanoemulsion carriers is their ability to deliver molecules in a wide
range of polarities.11,32These characteristics made the nanoemul-
sions a pretty fair delivery system for a variety of cosmetic for-
mulations. 26 Nowadays, nanoemulsions considered major delivery
systems for cleansing solutions, antiwrinkle formulas, and sun-
screens.4 Another advantage of using these nanoemulsions in skin
care products is providing a good contact of the actives to the skin
target (SC). This is because the particles provide a large surface
compared to the available volume. Another advantage of these small
particulates is enhancing the free flow of water and air molecules
between them, so no clogging to the pores will occur.
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3822      ABU HAJLEH et al.
NEs are bioactive molecules by themselves. They decrease the
trans-­epidermal water loss (TEWL) that, in turn, support the skin
11
barriers. Additionally, both droplets and surfactant molecules
might have interactions with the skin intracellular lipids. The inter-
action with the lipid structure will result in enhanced permeation
to the skin's upper layers. Skin hydration is encouraged by the oily
occlusive layer after distracting the cellular packing of the lipid bi-
layer component. Overall results are better topical absorption and
efficient skin hydration. 20,23
2.3.6  |  Cubosomes
Bi-­continuous crystals in a liquid state and their structured particles
are in nanoscale and arranged in a cubic manner. Many cosmeceuti-
cals could benefit from the use of these cubosomes. These include
skin and hair care products and hygienic products.10 Cubosomes
themselves act as stabilizers in emulsions and pollutant physical ab-
sorbents as well as in eco-­cosmeceuticals.13,27
2.4  |  Metal-­based nanosystems
Metal oxides evolved in cosmeceuticals and cosmetic preparations.
Skin and hair care products include sunscreen.33
2.4.1  |  Gold nanoparticles
Gold NPs have become valuable in cosmetic preparation (lotions,
antiaging creams, face packs, and deodorants) due to their action
34
against bacterial and fungal infections.  The diameter of these par-
21
ticles ranges from 1 to 100 nm. Different biological activities are
obtained by using gold nanoparticles such as rubefacient effect, en-
hancing the metabolism process of the skin, and retarding the aging
symptoms; also they possess some antiseptic and anti-­inflammatory
properties.35
2.4.2  |  Silver nanoparticles
Silver nanoparticles have a remarkable activity against biotic organ-
isms such as bacteria and fungus. Thus, they introduced extensively
in many cosmeceuticals and different formulations. Formulating
these nanoparticles into skin–­ointment dosage form has extra disin-
fectant benefits. On the other hand, silver NPs are also used in oral
cosmeceutical.36
2.4.3  |  Silica nanoparticles
Nanoparticles have a range of 5–­100 nm in diameter and could de-
liver substances in a wide range of lipophilicity into their active site
of action. Many cosmetics have been introduced silica NPs in their
formulations include skin, hair, and nail care products.6,9,37
2.4.4  |  Zinc oxide nanoparticles
Zinc oxide (ZnO) NPs are used in cosmetics, sun care, coatings, and
antibacterial. In cosmetics, it is mainly used in ointments, powders,
and creams. While it has UVA and UVB blocking properties, they
are used in different cosmetic formulations to protect from the
long-­term harmful effects of these rays such as skin aging and skin
cancer.38
2.4.5  |  Titanium oxide nanoparticles
Titanium oxide (TiO2) NPs are incorporated in many cosmetic prod-
ucts as UV filters. Titanium oxide is responsible for reflecting UVB
radiation. Therefore, the combined use of TiO2 and ZnO NPs pro-
vides an excellent protection against sun radiation without skin ir-
ritation, which is generally a significance of chemical UV filters.38
2.5  |  Additional nanosystems
2.5.1  |  Dendrimers
Dendrimers or fractal polymers are macromolecular with highly
branched artificial polymers with embedded architectures. 21
Dendrimers are spheres of symmetrical units in a diameter range
of 2–­20 nm.9,11 Many hairs, nail, and skin cosmetics used dendrimer
particles as their delivery system. 2,39 This system provides con-
trolled release of the drug and enhanced permeation of ACIs; sub-
sequently, improvement in both the entrapment capacity and the
product stability will be achieved.40
2.5.2  |  Fullerenes
Fullerenes have merged-­ring polycyclic systems which only com-
posed of an even number of carbon atoms. The carbons are arranged
either in a hollow spherical pattern, in oval or in tubes. Carbon fuller-
enes are highlighted in cosmetics due to their biological properties.
They claimed to have antioxidant, free radical scavenging, and UVA
blocking activities.41
2.5.3  |  Nanocrystals
In this nanosystem, hundreds to thousands of atoms are aggre-
gated in a single or poly-­crystalline form. the average diameter is
10–­4 00 nm. They are designed to deliver poorly soluble ingredi-
ents.13,27,42 M. Colombo et al., 2017 demonstrated that the solubility
ABU HAJLEH et al.
of dexamethasone and ibuprofen crystals (300 nm) was increased
in comparison to the solubility of drug particles with a size of 1mm
or larger.42
3  |  A PPLI C ATI O N S O F
N A N OTEC H N O LO G Y I N COS M EC EU TI C A L S
Not limited to beautifying reasons, the application of various NCs
formulations is introduced for some clinical and pathological cases.
These cases include hair loss, skin hyperpigmentation, and aging
symptoms resulted from photo-­oxidation.12 The efficacy of these
NCs is not exclusive to the active constituent; NCs carriers contrib-
uted to the biological activities.6
3.1  |  Nanotechnology for skin cosmeceuticals
2
Skin surface with around two m is the target of most cosmetic and
cosmeceuticals and considered as their main route of administration.
The release of the active ingredients from their carriers relied mainly
23
on their interaction with the skin.  Therefore, the application of
nanotechnology facilitates proficient skin penetration and enhances
the delivery of actives deep into skin layers, in particular, those tar-
geting the skin rejuvenating and revitalizing. The overall target is to
obtain healthy skin at a cellular level.9,11 For instance, the similar-
ity in lipid structures between skincare LPs and the epidermis could
improve the delivery into the target dermal layers and keep the sys-
temic absorption to a minimum. 26
3.1.1  |  Antiaging formulations
Several factors are responsible for the aging process, some of
them are genetics, and others are related to the environments.
Environmental factors including exposure to sun and pollutants,
lifestyle such as diet, and nicotine smoking are also considered fac-
tors. 26 Antiaging products formulated in nanotechnology can reach
deep layers in the skin to exert their action in minimizing fine lines
appearance.11 Antiaging formulas rely mostly on the biological action
of cosmeceuticals substances such as kinetin, vitamin A derivatives,
sunblocks, α-­tocopherol, ascorbic acids, coenzyme-­Q10, lipolic acid,
and other natural ingredients including the flavonoid resveratrol,
catechines from tea, and turmeric.43 Antiaging NCs formulations like
nanocapsules, LPs, nanosomes, and nanospheres amend the texture
of the skin texture in addition to its function that's by stimulating
collagen biosynthesis, maintaining the structure of keratin, firming,
and lifting the skin.44Preventing early symptoms of aging took place
by adding carbon fillers (C60) antioxidants to the skin formulations
aiming to rejuvenate the skin.45 Vitamins C and E are among the anti-
oxidant fullerene formulated in nanocapsules to achieve the desired
46
biological activity. Additionally, NEs contain ethanoic extractions
of natural products with well-­known antioxidant properties such as
|
      3823
quercetin and macela plant (Achyroclinesatureioides) have an extra
benefit in both delivering the actives and exerting its biological ef-
fects.47 Moreover, vitamin A-­loaded SLNs showed improved skin
occlusion when applied to porcine skin and could be utilized as a
powerful antioxidant for fighting skin aging.13
3.1.2  |  Antiwrinkles formulations
LPs originate from vegetable and soya phospholipids and contain
linoleic acid that helps in retarding wrinkle appearance and mini-
mize efflorescence in the treatment of acne leading to smoother
skin.48 Nanosomesporetinol antiwrinkle cream reduces the appear-
ance of wrinkles through enhancing collagen synthesis and increas-
ing epidermal water content. 2,10 Furthermore, retinyl palmitate NEs
showed increased skin penetration. Thus, they are considered pow-
erful antiaging ingredients that treat wrinkles by encouraging the
growth of new cells in the skin.13,49 Likewise, fillers formulated as
oil-­in-­water emulsion are used for all skin types and the treatment
of wrinkles.50 Rutin molecules formulated into nanocrystals acquire
500 times better bioavailability compared to regular aqueous formu-
lations; this indeed would increase the skin elasticity and decrease
aging dermal symptoms. 27,51
3.1.3  |  Skin clean formulations
Cleansing is necessary to remove debris, dirt, and odor from the
skin surface and maintain healthy skin. Micellar nanoparticles are
efficient carriers for different cosmeceuticals, in particular, skin
cleansers.4 For instance, silver nanoparticles act as disinfectants
and antiseptics. In addition, nanocyclic cleanser pink soaps, which
are made of a balanced mix of both phytomedicines and nanosil-
ver molecules, have antibiotic properties against any pathogens
include fungus and bacteria. The pink soaps could help in treating
acne and minimize the harmful effect of the sun on the exposed
skin.10
3.1.4  |  Sunscreen formulations
Ultraviolet (UV) radiations harm skin appearance and texture;
NCs products have remarkable protection effect against these ef-
fects.6,7,52,53 Sunscreen nanoparticles have a supreme effect over
other ordinary organic and inorganic sunscreens such as titanium
dioxide (TiO2) and benzophenones, respectively.52,54
Moreover, a synergism effect was noticed between the ac-
tual sunscreen particles and their nanocarriers since the carri-
ers themselves have sunblocking activity. 55 Therefore, both
SLNs and NLCs have a mastery role in sunscreen manufactur-
ing. 20 These two systems make a good combination with molecu-
lar sunscreens to avoid their undesired effects. 56 Also, SLNs tend
to perform as the carrier for other agents such as benzoylchitin
 |
3824      ABU HAJLEH et al.
derivatives and tocopherol and improve their photoprotection
57
activity. Quercetin SLNs attached with silica showed improve-
ment in both the bioavailability and photostability of quercetin. 58
Likewise, SLNs loaded with phytochemicals, such as caffeine,
lutein, and resveratrol, displayed enhancement in their bioavail-
ability and UV protection. 59,60
Interestingly, ZnO and TiO2 have the approval to be introduced in
sun protection formulas for their ability to reflect the UVA and UVB
rays to prevent away from skin's deep layers. As greasy, smelly, and
chalky appearance is the limitation of conventional sunblocks, those
formulated in nanotechnology overcome those problematic issues
10,61,62
and increase the customers’ acceptance and satisfaction.
vano et al. 2014 prepared phyto-­derived antioxidant noisome to
improve skin penetration. These noisome products contained sev-
eral antioxidants (resveratrol, curcumin, and alpha-­tocopherol) that
prevent photodegradation.63,64 On the other hand, Duarah et al.,
2016 explored the effect of tretinoin on the same activity; tretinoin
molecules were prepared as uni-­lamellar niosomes using Brij® deriv-
atives as a surfactant.65 It was also found that formulating genistein
isoflavone and tocomin, which are isolated from soya and red palm,
respectively, into NEs had increased cytoprotective activity after
long exposure to UVB. Curcumin as well showed better bioavailabil-
66,67
ity when formulated into NEs.
Introducing silica particles in sunscreens either as an emulsifier
agent in some formulas or as a water barrier in others has a good
impact on improving both the spreadability of the final product and
68
its safety profile. SLNs and NLCs have a special impact on skin-
care products in particular, moisturizers, that's due to their ability
to provide intimate contact with the skin and therefore better pen-
etration to the stratum corneum. 2 Not only for therapeutic activity,
but these tiny molecules also facilitate the penetration of the actives
into the skin layers, thus improving their hydration and aesthetic ap-
pearance. 25,69 It was found that adding 4% of SLNs to an ordinary
cream for a month would positively affect the skin hydration level
70,71
by 31%. LPs-­containing moisturizing creams were manufactured
using nanotechnology. Thus, LP component (phosphatidylcholine)
were used in numerous skin care moisturizers due to their softening
23,27,72
properties.
3.1.5  |  Skin-­whitening formulations
So and his colleagues reported the efficacy of quinazoline deriva-
tive as tyrosine inhibitor and whitening agents.73 Tyrosinase in-
hibitor was confirmed to hinder melanin synthesis and complete
induced pigments.74 Gold nanoparticles
the recovery from sun-­
(AuNPs) can also reduce the levels of melanin synthesis and affect
tyrosinase activity. Thus, it is proposed for the cosmetic applica-
tions of AuNPs. Therefore, the whitening effect of these was in-
9,73
vestigated.  Moreover, ginseng extract carried by NPs showed
whitening activity in addition to its confirmed anti-­inflammatory
properties according to the study published by Jiménez and his
colleagues.9
3.2  |  Nanotechnology for hair cosmeceuticals
Nanotechnology has a part in cosmeceuticals targeting hair. Hair
care products aimed to provide a shiny, glow, healthy, and smooth
appearance of hair shafts. 27 These products include cleansing and
conditioning agents, styling, and even hair growth stimulators.
Innovative carriers like niosomes, NEs, nanospheres, and LPs make
the hair non-­greasy and shiny and repair the damaged cuticles re-
sulting in restoring texture and gloss of the hair. Nanoparticles incor-
porated in shampoos offer a protective sealing film around the shaft
to achieve a longer contact time with the scalp and hair follicles. 75,76
Ta-
3.2.1  |  Hair general appearance improver
Nanomaterials of silicon oil have been incorporated in shampoos,
and this formula is considered gentle on the hair cuticle beside that
the nanoparticles permit the free penetration of the active ingre-
dients into the hydro-­lipid emulsion layer that in turn improve the
conditioning and glowing appearance.76 LP components (e.g., phos-
phatidylcholine) were also utilized in hair care conditioners and
shampoos as conditioning agents. 27 Nanoparticles can prevent hair
loss and maintain healthy hair.41 Sericin, derived from the silkworm,
nanoparticles are used in hair conditioners since these cationic NPs
have good adherence to hair seal surface, contributing to repairing
flaky cuticles and restoring hair gloss and texture.10,64,75 Carbonates,
phosphates, oxides, and hydroxides are all chemicals if formulated
into nanoparticles could be added to hair care products as excipi-
ents to control the grease of the hair. 29 According to Tomohiro et al.,
2018, improving the appearance of hair could be achieved by using
carbosiloxane dendrimer; it provides resistance to both water and
sebum and improves the glossiness, tactile sensation, and adhesive
properties of the hair. Carbosiloxane dendrimer use results in an
overall improvement in hair quality during its use.77
3.2.2  |  Hair coloring products
Nanotechnology has a role in permanent hair dye applications and
contributes to minimizing their toxicities. Nanotube's invention facil-
itates the stability and versatility of nanopigments; for instance, hal-
loysite clay nanotubes (HNT) which are derived from natural sources
could be loaded with pigments in basic colors such as red, blue, and
yellow, thus helping in optimizing the dye output and biocompat-
ibility.78 HNT technology has many advantages including decreasing
the harmful effect of dyes on the hair shaft as it decreases the direct
contact of the dying molecules with the shaft and ability to load dye
molecules from organic systems, and on top of it, the produce dye
coat could resist multiple washing, therefore prolonging the color
effect on the shaft.79 On the other hand, carbon black, the black
dye, used to cover grey hair has benefited from the application of
nanotubes. The nanosize of these carbon black molecules has better
interaction with the shafts, long-­lasting effects, and cleaner dye.80
ABU HAJLEH et al.
3.2.3  |  Hair growth and hair removal products
Nowadays, nanotechnology gives solutions to many technical and
formulation problems in hair care products. Hair growth stimula-
tors and hair removal products are among the cosmetics that use
nanotechnology. Fullerene nanostructures stimulate hair growth
and might encourage the formation of new follicles. These activi-
ties refer to their free radical scavenging activity though decreases
the oxidative stress consequences.75 Minoxidil has long been used
in the treatment of male baldness. Dryness, irritation, and burning
sensations are among the side effects of using minoxidil. Lipid nano-
particles overcome all these limitations; moreover, they improve the
81
permanence in the hair follicle region.
Finasteride stimulates hair growth by inhibiting the 5-­α reduc-
tase; it could also be applied less frequently and in lower doses, if
encapsulated into liquid crystalline nanoparticles for topical use. The
later formulation contributes to decreasing the undesired effects of
finasteride.75,82
Furthermore, the polymers that have a role in hair stimula-
tor products have enhanced activities when being formulated into
nanoparticles. The nanosized polymers have better permeability to
the scalp pores by 2–­2.5 times in addition to their improved activity.
Polylactic–­coglycolic acid is an example of polymer used, and hiokitiol
and gylcyrrhetinic acids are examples of active medications.83 On the
other side, hair removal agents were successfully carried by nanoma-
terials. The topical application of plasmonic nanoparticles is beneficial
in removing unwanted hair after being activated with light.84
3.3  |  Nanotechnology for nail cosmeceuticals
NCs have been efficient in the field of nail care products.
Nanotechnology contributes to the colored film toughness, durabil-
ity, and good elasticity. Also, the use of NCs in nail polish products in-
creases chip resistance and dryness time compared to conventional
products. 2 The antifungal properties of silver and metal oxide na-
noparticles were involved in treating infected toenails while apply-
ing products based on metal nanotechnology.85 Lau and colleagues
developed nail varnish products that incorporated metal NPs. This
invention has an added values of optical effects, color stability, chip
resistance, and antibacterial effects.86
3.4  |  Nanotechnology for lip cosmeceuticals
Many cosmetic agents targeting lips used NCs. These include lip-
sticks, glosses, balms, and even lip fillers. This technology aims to
soften the lips by decreasing TEWL and thus made the color last
longer.87 Lip volumizers having NCs LPs increase the lip volume,
2
keep the lips hydrated, and fill the wrinkles in the lip contour. Gold
and silver NPs provide a solution to lip pigmentation.88 A wide range
of safe colors were obtained by introducing NCs; for example, silver
NPs have a yellow color, while gold NPs are revealed red.
|
      3825
Consequently, different ratios of the nanoparticle carriers in-
volved in lip formulations result in a variety of colors within the vis-
ible spectra. Adding silica nanoparticles to the formulation prevents
color drifting to the lips corner and ensures color homogeneity.10
3.5  |  Nanotechnology for dental cosmeceuticals
The formulation of sulfide salts (ZnS and CdS) into nanoscale has
antimicrobial activities against variable oral pathogens. Pathogens
include candida, streptococcus, lactobacillus, and staphylococcus
species.89 Abrasive agents used in tooth whitening also could be
formulated in nanoscale, such as carbon NPs. The activated carbon
NPs protect from dental caries and fight plaques. These NPs have
superior effects on damaged enamel compared to the traditional
formula.9
3.6  |  Nanotechnology for beauty cosmeceuticals
Eye mascara has been formulated into NPs with the aid of ferric
oxide core by the green Chemical Common Tech Institute ®. This
novel mascara has a waterproof and long-­lasting effect. Morais and
colleagues developed sebum-­inhibitor products in a biocompatible
polymeric NP; the importance of this formula is enhancing the func-
tions of cosmetics by allowing the active ingredients to reach the
pores after minimizing the production of sebum.9 Also, skin founda-
tion with integrated NPs has better performance. The NPs designed
for this target use glycyrrhetinic acid encapsulated into the hydro-
phobic layer of silicon-­based chitosan. Once the polymer starts to
degrade, the ACI liberates and exhibits its role of regulating sebum
production.
4  |  TOX I CO LO G I C A L A S PEC T S O F
N A N O COS M EC EU TI C A L S
Following the definition of cosmeceuticals, no prescriptions are
needed as they have no therapeutic activities. These easily acces-
sible products have some acute and long-­term side effects which
might limit their applications. Concentration, duration, and the used
route of administrations are all factors affecting the side effects.
Nanostructures got access to human bodies through the respiratory
system by inhalation, through the gastrointestinal by ingestion and
dermally by direct contact.5Cosmeceuticals, which are intended to
be used on the lips or its contouring areas, have risks of systemic tox-
icities after accidental ingestion. These include sticks, glosses, and
coloring agents. The harm effects depend on variable factors; some
of them are related to the formulating properties of the active in-
gredients, such as their surface area, coating materials, particle size,
and aggregation tendency, while others are related to the chemical
composition of the cosmeceutical agent. If the nanostructure has
a matching surface with the organ, the hazard could be higher.90In
3826     |
general, increasing both chemical and biological reactivity is a reflec-
tion of increasing the ratio of surface area to volume. Therefore, na-
noparticles with poor solubilities exhibit pronounced toxicities and
related somehow to breast cancer.91 Sadly, lipid-­based NP carriers
of cosmeceutical show no safer profile due to its relative instabil-
92
ity.  Toxicities accompanied with fullerenes use are poorly under-
stood and need further investigations even though some primary
indications related their toxicities to their cell-­oxidizing activity.93,94
Titanium dioxide ultrafine particles could trigger inflammatory
reactions and cause injury to the lung tissue after pulmonary access.
Although metallic nanoparticles have antimicrobial activities, their
use associated with a decrease in RBC count, weight, and spleen
index, as shown in experimental animals.95 They are not safe to use
in pregnancy as they can cross the placenta.11,96 Formulas contain
zinc and titanium oxides that have membrane damaging effects
by generating free radicals, especially after exposure to UV light.
Dendrimers on their side harm cell membranes by interacting with
the phospholipid bilayers.97 To sum it all, using nanomaterials is as-
sociated with topical and systemic health hazards, and their safety
profile needs to be fully investigated.90,98
5  |   CO N C LU S I O N S
Nanotechnology is a key and essential technology that contributes
to the evolution of the cosmeceutical industry. This novel tech-
nology has better bioavailability, duration, and aesthetic appeal
compared to the conventional methods. Also, in economic-­wise, na-
noproducts have a reduced cost. Cosmeceuticals targeting skin, hair,
nail, lips, and dental care products have been incorporated into na-
nomaterials bases. These include lipid-­based NSs, polymeric-­based
NSs, metal-­based NSs, and additional NSs. These formulations are
intended for antiwrinkle, skin and tooth whitening, irregular pig-
mentation, dandruff, hair falls, and many other cosmetic products.
Recently, the expansion and growth of the cosmetic industry and the
introduction of nanotechnology in this industry evolve the urgent
need for scientific research and investigation of their safety profile
and caution of use. Tailored synthesis and formulation of these valu-
able nanomaterials for their intention of use are essential to keep
health hazards minimal.
C O N FL I C T O F I N T E R E S T
No conflict of interest was declared by the authors.
E T H I C S A P P R OVA L
Authors declare human ethics approval was not needed for this
study.
DATA AVA I L A B I L I T Y S TAT E M E N T
The datasets generated during and/ or analysed during the current
study are available from the corresponding author on reasonable
request.
ABU HAJLEH et al.
ORCID
Maha N. Abu Hajleh  https://orcid.org/0000-0001-5759-3538
Rana Abu-­Huwaij  https://orcid.org/0000-0002-0798-7069
Ali AL-­Samydai  https://orcid.org/0000-0003-0093-2310
Lidia Kamal Al-­Halaseh  https://orcid.org/0000-0002-2635-3619
Emad A. Al-­Dujaili  https://orcid.org/0000-0002-0985-7217
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How to cite this article: Abu Hajleh MN, Abu-­Huwaij R,
AL-­Samydai A, Al-­Halaseh LK, Al-­Dujaili EA. The revolution of
cosmeceuticals delivery by using nanotechnology: A narrative
review of advantages and side effects. J Cosmet Dermatol.
2021;20:3818–­3828. https://doi.org/10.1111/jocd.14441