REVIEW ARTICLE

Lipid Nanoparticle a Novel Carrier for Cosmetics and Topical

Preparation: A Review
Dilip Patel1*, Vikash Kumar1, Roohi Kesharwani2, Bhaskar Mazumdar3
Abstract: Lipid nanoparticles are an alternative carrier system to liposomes and emulsions. This review paper focuses on lipid
nanoparticles for cosmetic and topical application. Production of lipid nanoparticles and final products containing lipid
nanoparticles is feasible by well-established production methods. Lipid nanoparticle exhibit many features for topical
application of cosmetics and pharmaceutics, i.e. controlled release of actives, Physical and chemical stability of active
pharmaceutical ingredients, drug targeting, occlusion, film formation and associated with it penetration enhancement and
increase of skin hydration. Due to the production of lipid nanoparticles from physiological and/or biodegradable lipids, this
carrier system exhibits an excellent tolerability. The lipid nanoparticles are a “nanosafe” carrier. Furthermore, an overview of
the cosmetic products currently on the market is given and the improvement of the benefit/risk ratio of the topical therapy is
shown.

INTRODUCTION are loaded with keratin filaments and surrounded by a cell

The use of solid lipid matrices is known in pharmacy for envelope composed of cross-linked proteins (cornified
many years, e.g. drug release from lipid pellets. Solid lipid envelope proteins) as well as a covalently bound lipid
mircoparticles were introduced by Speiser. [1] In the next envelope. Extracellular non-polar lipids surround the
step the size of the particles was further reduced to the corneocytes to form a hydrophobic matrix.
nanosize yielding the lipid nanoparticles, the SLN and as a During the final stages of normal differentiation,
further development of the SLN the NLC. For topical keratins are aligned into highly ordered and condensed
applied lipid nanoparticles all excipients, which used in the arrays through interactions with filaggrin, a matrix protein.
current topical cosmetic and dermal pharmaceutical The role of filaggrin in skin barrier homeostasis is only
products, can be used. In addition, GRAS substances and partially known. Filaggrin aggregates the keratin filaments
substances with accepted GRAS status can be used. The into tight bundles. This promotes the collapse of the cell
choice of the lipid matrix and surfactant is essential in into a flattened shape, which is characteristic of
order to formulate an optimal safe and stable formulation. corneocytes in the cornified layer. [5] Together, keratins and
[2]
filaggrin constitute 80–90% of the protein mass of
mammalian epidermis. [6] Skin is a widely used route of
SKIN: THE BARRIER delivery for local and systemic drugs and is potentially a
The skin (Latin: cutis) consists of 250 Am (<4000 Am) thick route for their delivery as nanoparticles. Whilst
inner skin region (=dermis) and of 50 Am (<100 Am) thick nanoparticle drug delivery has been touted as an enabling
outer skin region (=epidermis). The fact that the skin is one technology, its potential in treating local skin and systemic
of best biological barriers is mainly due to the outermost diseases has yet to be realised. Most drug delivery particle
part of the epidermis, the skin horny layer (Latin: the technologies are based on lipid carriers, i.e. solid lipid
stratum corneum, SC). [3] The SC serves as the principal nanoparticles and nanoemulsions of around 300 nm in
barrier against the percutaneous penetration of chemicals diameter, which are now considered microparticles.
and microbes and is capable of withstanding mechanical The skin has historically been used for the topical
forces. [4] It is further involved in the regulation of water delivery of compounds but it is only since the 1970s with
release from the organism and into the atmosphere, known the advent of transdermal patches that it has widely been
as transepidermal water loss (TEWL). The SC forms a
used as a route for systemic delivery. Nanoparticle delivery
continuous sheet of protein-enriched cells (corneocytes)
to the skin is being increasingly used to facilitate local
connected by corneodesmosomes and embedded in an
therapies. The nanoparticle definition designated by the
intercellular matrix enriched in non-polar lipids and
National Nanotechnology Initiative has been adopted by
organized as lamellar lipid layers. The final steps in
the American National Standards Institute as particles with
keratinocyte differentiation are associated with profound
all dimensions between 1 nm and 100 nm. This shows that
changes in their structure, resulting in their transformation
the potential sites for targeting nanoparticles include the
into the flat and anucleated corneocytes of the SC, which
surface of the skin, furrows and hair follicles. [7] A recent
review by Baroli discusses nanoparticle penetration largely
1Department of Pharmaceutical Sciences, Faculty of Health Sciences, from the skin structure perspective debate of nanoparticle
SHIATS, Naini, Allahabad- 211008, Uttar Pradesh, India.
E-mail: [email protected]
penetration. [8]
*Corresponding author
Stratum Corneum: Barrier and Reservoir Function
2Dayanath Dinanath College of Pharmacy, Kanpur- 208002, Uttar Pradesh, To be well absorbed, a substance should have a molecular
India.
mass less than 0.6 kDa, adequate solubility in oil and water
3Department of Pharmaceutical Sciences, Dibrugarh University, and a high partition coefficient. Moreover, it should be
Dibrugarh-786004, Assam, India. applied as a saturated or even better supersaturated

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 REVIEW ARTICLE

Figure 1: Triggered drug release and super saturation effect. Drug loaded NLC are incorporated into an o/w cream [11]

Figure 2: Mechanism of drug expulsion during storage of SLN dispersions, transition to highly ordered lipid crystal [14, 15]

system. Although a partially disturbed barrier in many skin reported to be embedded into the solid lipid matrix or to be
diseases (e.g. atopic eczema and psoriasis) can favour API localised at the surface of solid platelets and the surfactant
permeation through the horny layer, adequate skin layer.
penetration is still an important challenge in the The penetration of active compounds into human skin
development of topical dermatics. Conventional drug was studied using the Tesa stripping test investigated
carrier systems, such as creams and ointments, result in compounds included coenzyme Q10 and retinol. The
API uptake of only a few percent, which moreover as a rule coenzyme Q10 was dissolved in isopropanol, in liquid
is linked to a rather high inter individual variation of paraffin or applied as an aqueous SLN dispersion. This
uptake rates. Consequently, API levels within the diseased shows the cumulative amount of the compound in the
skin may be sub-therapeutic in some patients while strips as a function of the strip number. SLN proved to be
inducing unwanted local or systemic side effects in others. most efficient in promoting penetration into the stratum
Moreover, highly lipophilic compounds can penetrate via corneum. For cosmetic products, it is important that the
the hair follicle. Follicular uptake may be most relevant active compounds stay in the skin, penetrate sufficiently
with rigid API crystalline particles and particulate carriers deep but not too deep leading to systemic availability.
with a size of 3–10 μm. Other than with the horny layer, Penetration should be sufficient to lead to a cosmetic effect
micrometer size does not exclude penetration into but not a pharmaceutics effect. Penetration studies with
follicular orifices. Besides acting as a permeation barrier, drugs in pharmaceutical dermal formulations revealed that
the horny layer is also a reservoir for topically applied the degree of penetration obviously depends on the
substances. For example, four days after the application of chemical composition of the formulation. In-vitro skin
glucocorticoids under occlusion, vasoconstriction could be penetration studies were also per-formed in NLC using
re-induced by renewed occlusion of the treatment area. retinol as the compound of interest for cosmetics and
More recently, a saturable uptake of UV filters was pharmaceuticals. The studies revealed a different
described. Investigations with primaquine demonstrated penetration profile compared to the nanoemulsion used as
that both binding to corneocyte keratin as well as the reference. Initially, the concentrations were lower (due to
miscibility of the drug with the lipid domains contribute to prolonged release from particle), after a 24-h period,
the horny layer reservoir. [9, 10] higher retinol levels were found in the residual skin. The
studies were performed using the Franz cell model and
COSMETIC AND TOPICAL BENEFITS OF LIPID porcine skin. Preparation of the particles with this
NANOPARTICLE relatively high amount of oil led to the formation of oil
Improved Skin Penetration nanocompartments, which means the solid lipid
Solid lipid nanoparticles (SLN, Nanopearls®) are made of nanoparticle investigated was in fact an NLC type 3. The
lipids solid at room temperature, the surface being covered flux of retinol from lipid particle dispersion was compared
by a surfactant (tensid, emulsifier) shell which stabilizes to the flux of retinol from an o/w nanoemulsion which
the dispersion. Nanostructured lipid carriers (NLC) are served as control (identical composition, solid lipid
mixtures of solid and fluid lipids, the fluid lipid phase is replaced by Miglyol 812). The flux of retinol from the

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 REVIEW ARTICLE

nanoemulsion system remained unchanged during the stability in these systems. The SLN and NLC remain as
investigated period. Due to increased order and increased definite particles during the storage time. [19, 20]
expulsion of drug the flux increased from the nanoparticle It was found that the higher concentrated particle
dispersion. [11, 12] dispersions showed sufficient physical stability during
storage whereas low concentrated ones aggregated. Lipid
Loading Capacity Nanoparticle dispersions with increasing lipid content
A major drawback of SLN is the frequently low loading were produced. The higher concentrated were practically
capacity which is limited to about 10% of the amount of unchanged in size during storage avoiding the problems of
lipid (leading to about 1% of the final dispersion) to ensure lower concentrated dispersions The explanation is that in
stability of the system . This is due to the specific nature of the low concentrated particle dispersions, the particles are
the solid lipid matrix and holds true especially with APIs of freely diffusible can collide and aggregate. In the highly
only moderate lipophilicity. Therefore both the physico- concentrated dispersions, the particles are fixed in the
chemical parameters of active agent and lipid have to be pearl-like network diffusion and subsequent aggregation is
considered. The review by Mehnert [13, 9] high lights these reduced. [11]
aspects; Pay-load for a number of drugs too low and Drug
expulsion during storage (Figure 2). Film Formation and Occlusive Property
NLC have been developed to overcome the drawbacks The stratum corneum contains 10-20% water. If the water
associated with SLN. They are considered to be the second content falls below this value (i.e., if water evaporation
generation of lipid nanoparticles. Compared to SLN, NLC from the skin to the atmosphere is increased) the
show a higher loading capacity for active compounds by protective layer of the skin is no longer intact and starts to
creating a less ordered solid lipid matrix, i.e. by blending a get chapped. In this case, occlusive topicals have to be
liquid lipid with the solid lipid, a higher particle drug applied in order to regenerate the water content of the
loading can be achieved. Therefore, the NLC have an stratum corneum and thus repair the surface of the skin.
increased drug loading capacity in comparison to SLN and Due to occlusion water Evaporation from the skin to the
the possibility of drug expulsion during storage is less. [14, atmosphere is decreased and water is thus retained within
16] the skin. The stratum corneum swells, which leads to a
drug permeation enhancing effect. However, many of the
Improved Chemical Stability topical with good occlusive properties (e.g., petrolatum,
The solid matrix of SLN can protect labile APIs from fats, fatty acids) have an unacceptable Cosmetic or
hydrolysis and oxidation. This is of relevance for topical aesthetic appearance. Therefore different w/o and o/w
agents used for antiaging and mild acne. SLN improve the emulsions have been developed. They represent a
chemical stability of tocopherol, retinol and coenzyme Q10 compromise between occlusive performance and
as compared to an aqueous dispersion tocopherol by 57%. appearance on the skin. The occlusive character of SLN is
[9, 17] A much more sensitive cosmetic molecule is retinol. due to film formation after application to the skin, leading
Under the influence of light and oxygen, it decomposes to a to decreased water evaporation. [21, 22] Souto et al., [23] found
variety of structures, e.g. different epoxy retinoids. The a higher occlusive factor for SLN in comparison to NLC of
stabilization effect of SLN on retinol was investigated using the same lipid content. Comparing NLC with different oil
different lipids as matrix material and different surfactants content showed that an increase in oil content leads to a
and surfactant mixtures. Firstly, the study revealed that the decrease of the occlusive factor.
stabilization effect differed between the lipids used, this
indicates that for very sensitive molecules, the lipid has to Skin Hydration and Elasticity
be selected carefully. Unfavorable lipids (e. g. too acidic The reduction of trans epidermal water loss (TEWL)
lipids) can lead to a less pronounced stabilization. caused by occlusion leads to an increase in skin hydration
Secondly, different extents of stabilization were observed after dermal application of SLN, NLC or formulations
as a function of surfactant. [11, 18] containing them. An in-vivo study showed that the SLN
containing o/w cream increased the skin hydration
Improved Physical Stability significantly more than the conventional o/w cream. In this
The liposomes represent the most innovative cosmetic study the skin hydration effect after repetitive application
carrier system of the 1980s, introduced to the market by of an o/w cream containing SLN and a conventional o/w
the company Dior in 1986 (product “Capture”). Despite the cream was investigated for 28 days. A significant higher
many positive features, a major problem up today is the increase in skin hydration was found by Müller et al., [19] for
limited physical stability of liposomes in the presence of oil an NLC-containing cream compared to conventional cream.
emulsion droplets and surfactants. The liposomes tend to
fuse with each other and with the surfactant layer of oil Enhanced Skin Bioavailability of Actives and Skin
droplets. The number of liposomes in o/w formulations is Targeting
steadily decreasing with increasing shelf-life. Approaches Cosmetic actives should localize in the skin but not cause
of increasing the rigidity of the liposomal bilayer could only any systemic effects to avoid crossing the border between a
delay but not avoid this effect. A major advantage of lipid cosmetic and a pharmaceutical formulation. Therefore, a
nanoparticles with solid matrix is their high physical certain penetration into the skin is desired, especially the

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 REVIEW ARTICLE

Table 1: Marketed Finished Cosmetic Products

Product Name Producer/Distributor Date of Market Launching

Cutanova Cream Nano Repair Q10 Dr. Rimpler 10/2005
Cutanova Cream NanoVital Q10 Dr. Rimpler 06/2006
Intensive Serum NanoRepair Q10 Dr. Rimpler 10/2005
SURMER Crème Legère Nano-Protection Isabelle Lancray 11/2006
SURMER Crème Riche Nano-Restructurante Isabelle Lancray --------
SURMER Elixir du Beauté Nano-Vitalisant Isabelle Lancray ---------
SURMER Masque Crème Nano-Hydratant Isabelle Lancray ---------
NanoLipid Restore CLR Chemisches Laboratorium 04/2006
Nanolipid Q10 CLR Dr. Kurt Richter, (CLR) 07/2006
Nanolipid Basic CLR Dr. Kurt Richter, (CLR) 07/2006
NanoLipid Repair CLR Dr. Kurt Richter, (CLR) 02/2007
IOPE SuperVital Amore Pacific 09/2006
Cream,Serum Amore Pacific
Eye cream Amore Pacific
Extra moist softener Amore Pacific
Extra moist emulsion Amore Pacific
NLC Deep Effect Eye Serum Beate Johnen 12/2006
NLC Deep Effect Repair Cream Beate Johnen
NLC Deep Effect Reconstruction Cream Beate Johnen
NLC Deep Effect
Reconstruction Serum Beate Johnen 05/2007
hexapeptide-8, higly active oligosaccharides
NLC Deep Effect launch 2007
Regenerationscreme Intensiv Scholl 03/2007
Swiss Cellular White Illuminating Eye Essence La prairie 01/2007
Swiss Cellular White Intensive Ampoules La prairie
SURMER Crème Contour Des Yeux Nano-
Isabelle Lancray 03/2008
Remodelante
Olivenöl Augenpflegebalsam Dr. Theiss 02/2008
Olivinol Augenpflegebalsam Dr. Theiss

active should be localized in the skin. The same is valid for and etomidate are released spontaneously from the solid
many pharmaceutical actives, e.g. corticoids. Localization in lipid matrix an initial burst release is followed by a
the upper skin minimizes side effects such as skin thinning. prolonged release for several days or even six weeks, as
For the corticoid prednicarbate it could be nicely shown demonstrated with prednisolone and clobetasole
that the drug localizes more in the upper skin compared to propionate, respectively. [9, 26, 27]
an emulsion based formulation occlusion (e.g. plastic foil
onto cream applied to skin) promotes the penetration of Novel Technique Applicable for Production
actives into the skin. Increased penetration of coenzyme Q Lipid nanoparticles are prepared from lipid, emulsifier and
10 was described after application of a Q 10-loaded SLN water/solvent by using different methods and are
suspension in comparison to solutions of isopropanol and discussed below: [28]
liquid paraffin. Penetration into the skin was determined 1. High pressure homogenization
by a tape stripping test (Scotch® tape). The cumulative a. Hot homogenization
amount of the first 5 strips was 53% for the SLN b. Cold homogenization
suspension, 30% for isopropanol and just 2% for liquid 2. Ultrasonication/high speed homogenization
paraffin, calculated in % of applied dose. [19, 24] 3. Solvent Emulsification Evaporation Technique
4. Solvent emulsification-diffusion method
Controlled Release of Cosmetic Compound 5. Supercritical fluid method
The perfume Allure was incorporated in SLN and the 6. Microemulsion based method
release studied compared to a nanoemulsion of identical 7. Spray drying method
lipid content and surfactant composition. The initial release 8. Double emulsion method
was similar, most likely due to perfume present in the 9. Precipitation technique
outer shell of the SLN. During the follow-up period to 8 h, 10. Solvent injection technique
release from the SLN was delayed. This opens the prospect 11. Membrane contractor technique
of developing longer lasting perfume formulations based 12. Film-ultrasound dispersion.
on the prolonged release of the perfume from the solid lipid
matrix. [11, 25] Lipid Nanoparticle as Novel UV Sunscreen System
Drug release from SLN has been evaluated using The two basic UV protection systems are molecular UV
steroids as well as other agents as model drugs. Tetracain blockers (sunscreens) and particulate compounds such as

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 REVIEW ARTICLE

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