Inclusion of lipid nanoparticles in skin care products

Inclusion of lipid nanoparticles in skin care products
  1. Lipid nanoparticles

Lipid nanoparticles have been intensively studied for numerous applications, such as parenteral, oral, ocular, cutaneous and pulmonary administration.  However, has been given particular attention to cutaneous application, which is probably the one that has been most studied.

In the early nineties of the twentieth century, Solid Lipid Nanoparticles (SLN) were developed as an alternative to emulsions, liposomes and polymeric nanoparticles. Furthermore, a new generation of lipid nanoparticles called Nanostructured Lipid Carriers (NLC) was also developed, using blends of liquid and solid lipids. However, these nanoparticles remain solid at room and body temperature as the SLN which are manufactured using only solid lipids.  Both SLN and NLC show advantageous characteristics for cutaneous application such as a controlled release of the active, good tolerability, a narrow contact with stratum corneum and an increase in skin hydration. Additionally, lipid nanoparticles are able to increase chemical stability of active ingredients against light, oxidation and hydrolysis (1-4).

There are many different techniques described in the literature for the production of lipid nanoparticles, however, the most used include the high shear homogenization and ultrasound, and high pressure homogenization (5-9). Commonly, lipid nanoparticles are obtained by mixing the melted lipid with an aqueous medium containing a surfactant, followed by application of mechanical forces (ultrasounds or high pressure) to break the oil droplets at a nanometer size. Upon cool to room temperature, these droplets solidify into nanoparticles. The final product is a milky dispersion, containing the lipid nanoparticles dispersed into the aqueous medium.

  1. Suitable formulations for skin application

The most common topical formulations present a semisolid consistency. Considering the physical properties of topical formulations, with special emphasis in rheology, formulations presenting non-Newtonian shear-thinning (or pseudoplastic) behavior are preferred for skin application. The shear-thinning behavior is characterized by a decrease in viscosity values with increase of shear rate, meaning an easy spreadability of the product on the skin (10). Thixotropy, a reversible variation of viscosity with time is desirable in topical formulations, because it could facilitate the application of the product on the skin surface (11).

The obtained colloidal dispersions of lipid nanoparticles with null consistency, presenting a Newtonian behavior, are not suitable systems for skin application. This means that aqueous dispersions of lipid nanoparticles need to be included in a semisolid formulation allowing their application on the skin. The semi-solid formulations can be obtained by incorporation of the aqueous dispersions in dermatological bases (e.g. creams) or through the addition of viscosifying agents obtaining a gel. Addition of lipid nanoparticles to creams can be performed during or after the production of this dermatological base. The second approach has more advantages for the incorporation of lipid nanoparticles because the cream is produced as usual, but with reduced water content in order to compensate the water added with the aqueous dispersion. After production of the cream, the colloidal dispersion is mixed by stirring at room temperature. This process avoids the melting of the nanoparticles, which could lead to an undesirable change of the internal particle structure and at room temperature the particles are sufficiently stable avoiding coalescence with oil droplets of the internal phase of the semisolid emulsion (cream). In the case of the addition, of viscosifying agents two possibilities can be considered: direct addition of the viscosity enhancer (xanthan gum, cellulose polymers, carbomers or chitosan) to the nanoparticles dispersion or preparation of a hydrogel more concentrated followed by mixture of the nanoparticles dispersion with the gel by stirring. In both cases, studies have shown that the final formulations containing the lipid nanoparticles present a shear-thinning behavior with thixotropy, whereas the corresponding gels without nanoparticles do not present thixotropy (7, 12, 13).

  1. Marketed formulations based on lipid nanoparticles

An interesting example that could be cited is the case of NanoLipid Restore CLR® developed by Chemisches Laboratorium Dr. Kurt Richter, Germany and distributed by Pharmacos India. NanoLipid Restore CLR® consists of a white to light yellow liquid NLC dispersion containing black current seed oil, as a liquid lipid. This oil is rich in ω-3 and ω-6 fatty acids, being this product designed for regenerative care of dry, scaly, rough and aged skin, restoring the skin barrier and reducing transepidermal water loss (TEWL). Additionally, the NLC technology is able to protect the fatty acids against oxidation and permits a controlled release of the incorporated black current seed oil. Other components of this dispersion include carnauba wax as a solid lipid, decyl glucoside as a surfactant and water. NanoLipid Restore CLR® is a semi-finished product used in the cosmetic product line IOPE® from Amore Pacific, South Korea.

Additionally, other products containing NLC are in the market such as Nanorepair Q10® (cream and serum) and Nanovital Q10® (cream) from Cutanova® (Dr.Rimpler, Germany) and Surmer® from Isabelle Lancray (France) (14).

Dr. Marilene Sofia Rodrigues Estanqueiro is speaking at the Delivery systems for cosmetic actives: How to deliver your actives through the skin barrier to their site of action workshop at in-cosmetics on Wednesday 15 April 2015, 14:00 – 17:30 Workshop Room CC5.3


  1. Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366:170-84.
  2. Muchow M, Maincent P, Müller RH. Lipid Nanoparticles with a Solid Matrix (SLN®, NLC®, LDC®) for Oral Drug Delivery. Drug Dev Ind Pharm. 2008;34:1394-405.
  3. Radtke M, Souto EB, Müller RH. Nanostructured Lipid Carriers: A Novel Generation of Solid Lipid Drug Carriers. Drugs Made Ger. 2005;17(4):45-50.
  4. Puglia C, Blasi P, Rizza L, Schoubben A, Bonina F, Rossi C, et al. Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo investigation. Int J Pharm. 2008;357:295-304.
  5. Puglia C, Blasi P, Rizza L, Schoubben A, Bonina F, Rossi C, et al. Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo investigation. Int J Pharm. 2008;357(1-2):295-304.
  6. Silva AC, Amaral MH, Gonzalez-Mira E, Santos D, Ferreira D. Solid lipid nanoparticles (SLN)–based hydrogels as potential carriers for oral transmucosal delivery of risperidone: preparation and characterization studies. Colloids Surf B Biointerfaces. 2012;93:241-8.
  7. Estanqueiro M, Conceição J, Amaral MH, Sousa Lobo JM. Characterization, sensorial evaluation and moisturizing efficacy of nanolipidgel formulations. Int J Cosmet Sci. 2014;36(2):159-66.
  8. Jenning V, Lippacher A, Gohla SH. Medium scale production of solid lipid nanoparticles (SLN) by high pressure homogenization. J Microencapsul. 2002;19(1):1-10.
  9. Souto EB, Müller RH. Investigation of the factors influencing the incorporation of clotrimazole in SLN and NLC prepared by hot high-pressure homogenization. J Microencapsul. 2006;23(4):377-88.
  10. Marty JP, Lafforgue C, Grossiord JL, Soto P. Rheological properties of three different vitamin D ointments and their clinical perception by patients with mild to moderate psoriasis. Journal of the European Academy of Dermatology and Venereology. 2005;19:7-10.
  11. Korhonen M, Hellen L, Hirvonen J, Yliruusi J. Rheological properties of creams with four different surfactant combinations – effect of storage time and conditions. Int J Pharm. 2001;221:187-96.
  12. Tichota DM, Silva AC, Sousa Lobo JM, Amaral MH. Design, characterization, and clinical evaluation of argan oil nanostructured lipid carriers to improve skin hydration. Int J Nanomedicine. 2014;9:3855-64.
  13. Silva AC, Amaral MH, González-Mira E, Santos D, Ferreira D. Solid lipid nanoparticles (SLN) – based hydrogels as potential carriers for oral transmucosal delivery of Risperidone: Preparation and characterization studies. Colloids Surf B Biointerfaces. 2012;93(0):241-8.
  14. Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366:170–84.

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