Nanostructured lipid carriers (NLC) in cosmetic dermal products

https://doi.org/10.1016/j.addr.2007.04.012Get rights and content

Abstract

The first generation of lipid nanoparticles was introduced as solid lipid nanoparticles (SLN), the second, improved generation as nanostructured lipid carriers (NLC). Identical to the liposomes, the lipid nanoparticles (NLC) appeared as products first on the cosmetic market. The article gives an overview of the cosmetic benefits of lipid nanoparticles, that means enhancement of chemical stability of actives, film formation, controlled occlusion, skin hydration, enhanced skin bioavailability and physical stability of the lipid nanoparticles as topical formulations. NLC are on the market as concentrates to be used as cosmetic excipients, special formulation challenges for these products are discussed. NLC appeared also in a number of finished cosmetic products world-wide. An overview of these products is provided including their special effects due to the lipid nanoparticles, lipids used for their production and incorporated cosmetic actives.

Introduction

Lipid nanoparticles with solid particle matrix are derived from o/w emulsions by simply replacing the liquid lipid (oil) by a solid lipid, i.e. being solid at body temperature. The first generation of solid lipid nanoparticles (SLN) was developed at the beginning of the nineties [1]. They were produced from a solid lipid only. In the second generation technology of the nanostructured lipid carriers (NLC), the particles are produced by using a blend of a solid lipid with a liquid lipid, this blend also being solid at body temperature [2].

The production process is identical for both particles SLN and NLC. The solid lipid or lipid blend is melted, the pharmaceutical or cosmetic active dissolved in the melted lipid phase which is subsequently dispersed by high speed stirring in a hot aqueous surfactant/stabilizer solution of equivalent temperature. The obtained pre-emulsion is homogenized in a high pressure homogenizer yielding a hot o/w nanoemulsion. After cooling the emulsion droplets crystallize forming lipid nanoparticles with solid particle matrix, depending on the starting material either SLN or NLC.

The advantage of the second generation technology is the increased loading with actives compared to SLN and firmer inclusion of the active inside the particle matrix during the shelf life. By preparing the particles from a solid lipid, especially highly purified solid lipids, the particle matrix tends to form a relatively perfect crystal lattice leaving limited space to accommodate the active (Fig. 1, left). This limits the loading capacity and can lead to expulsion of active from the lipid matrix during storage [3]. In contrast, the use of a lipid mixture with very differently structured (sized) molecules distorts the formation of a perfect crystal. The particle matrix contains many imperfections providing space to accommodate the active in molecular form or as amorphous clusters (Fig. 1, right). One could state that “the perfectness” of the NLC system is its “imperfectness” in its crystalline structure.

In the second half of the nineties there was an increasing interest in investigating the SLN for dermal application, especially for cosmetic use. Interesting cosmetic molecules were incorporated such as e.g. retinol and retinylpalmitate [5], vitamin E and vitamin E acetate [6] and coenzyme Q 10 [7]. An example for pharmaceutical actives is the incorporation of corticoids, such as prednicarbate [8]. At the turn of the millennium the NLC were developed [9] which – based on the controlled nanostructuring of the particle matrix – provide advantages with regard to loading capacity and long-term stability (firm inclusion of actives, physical stability of suspension). For cosmetic applications requiring a high crystallinity of the carrier (e.g. UV protection), SLN are still a suitable carrier. However, for many cosmetic applications NLC are preferable, therefore development of cosmetic products in the new millennium concentrated on the NLC system.

Historically at the beginning research with SLN focussed on their use as intravenous/parenteral drug carrier, gradually interest shifted to lipid nanoparticles for oral administration and later on for dermal application. One of the reasons is that the regulatory hurdles are lower for oral, especially for dermal products, allowing a faster introduction of the carrier system to the market. Comparing lipid nanoparticle formulations for dermal application in the pharmaceutical and the cosmetic field, there is basically little difference regarding technological aspects (e.g. incorporation of actives into particles, incorporation of particles into cream, stability in cream etc.). However, the time for product development and market introduction for cosmetic products is much shorter; consequently the first NLC products appearing on the market were cosmetic products. This article reviews the cosmetic benefits of NLC in general, and especially technological aspects and special features of the cosmetic products available by now, consideration is given to technological challenges when moving from lab scale to a large scale production. It should be emphasized that the formulation and technological aspects have also a high relevance for upcoming pharmaceutical dermal products.

Section snippets

Enhancement of chemical stability of actives

O/w emulsions and liposomes belong to the most frequently employed carriers for the delivery of cosmetic actives. However they are not, or only to a limited extent, able to protect chemically labile actives against degradation. Due to the liquid character of oil droplets in o/w emulsions, fast partitioning of lipophilic actives between oil phase and water takes place. The active is degraded in the water phase, re-partitions into the oil phase and being replaced in the water phase by

General aspects of formulating NLC products

One approach to create NLC cosmetic products is admixing concentrated NLC suspensions to established products on the market. The products are produced as usual with a reduced amount of water, this amount of water is then replaced by a concentrated NLC suspension. Typically the creams and lotions are produced, cooled to about 30 °C, and the concentrated NLC suspension is admixed by applying gentle stirring. The smart aspect of this approach is that the positive features of an already established

NanoRepair Q 10 Cream and Serum

The first two world-wide finished products with NLC, NanoRepair Q 10 Cream and NanoRepair Q 10 Serum, were introduced to the market by the German company Dr. Rimpler GmbH (Wedemark near Hannover/Germany, www.rimpler.de). Market introduction took place at the cosmetic fair “Beauty” in Munich October 2005. The NLC particles contain a relatively high loading of coenzyme Q 10. The final concentrations of coenzyme Q 10 are 0.5% in the cream and 0.1% in the serum. Coenzyme Q 10 is a relatively

Conclusion and perspectives

Since about 20 years after the introduction of the liposomes the cosmetic market is waiting for a similar innovative novel nanocarrier, but possessing improved properties. All systems developed since 1986 were far away from the success of the liposomes. The lipid nanoparticles, both SLN and NLC, possess many of the positive advantages of the liposomes and in addition features being clearly superior to liposomes.

The success of a delivery system can be judged firstly by the time passed between

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