Precise delivery of actives: COSSMA

Liposomes are used so that active ingredients can penetrate exactly into the skin layer intended for them and act there. Daniel Pando and Dr Jörg Oliver Schmitz talk about their different capabilities depending on the size and composition of the Liposomes.

Liposomes are systems able to encapsulate cosmetic actives. Because of their protection and vehiculation capacity, liposomes increase the effectiveness of the cosmetic actives. Recent developments in the formulation of liposomes allow a more precise target-oriented delivery than ever before in cosmetic history. The first liposomes were developed in the 1960s in the University of Cambridge laboratories by Professor Bangham. His initial objective was to disperse lipophilic compounds (encapsulated in liposomes) in aqueous solutions. In 1986, impressed by their results, the laboratories of Christian Dior developed the first cosmetic product based on liposomes. The presence of liposomes in other fields has grown year after year while they have evolved in the most innovative laboratories. Liposomes are currently used in various fields, of which the most prominent are medicine, cosmetics, and food.

What is a liposome?

A liposome is a spherical nanovesicle formed mainly by phospholipids, which adopt a lipid bilayer structure when they are in aqueous dispersions. According to EC Regulation 1223/2009 on cosmetic products it isno nanomaterial. Liposomes normally have sizes slightly larger than 100 nm (means: not nanomaterial). Even if they are below this size, they would still maintain their non-nanomaterial status since they are soluble and biodegradable.

figure 1: Structure of a a liposome. figures: Indermal/nanovex Biotechnologies

Changes in technology

The technology today is absolutely not the same as that of the ‘60s or '80s. Although the concept and the base (phospholipids) are similar, liposomes have evolved (and will continue to do so) in terms of composition and manufacturing methods, among others.

Such is its evolution that a large part of the new drugs which are being developed for the future are based on this technology. The current liposomes are quite different to those developed by Bangham in the 1960s. Main advantages in cosmetics The most important advantages are the protection of the encapsulated compound, preventing its degradation, and the ability to transport and release it in the target skin layers, increasing the payloads efficiency. In case of the latest developments, another big advantage is the increased precision of target oriented modern liposomes which allows for more efficient use of actives, thus reducing the amount needed to achieve a desired efficacy, and consequently reduces undesired side effects. Other advantages are the possibility of dispersing lipophilic compounds in aqueous phases and the masking of odours and colours, among others. In addition, the liposome composition repairs the protective barrier and contributes to maintaining hydration.

Several types of liposomes

Considering both its composition and its morphology, we can find many variants. Regarding its composition, the fundamental compound is phospholipids. These compounds can be incorporated either using lecithin (which contains between 50-70% phospholipid mixtures) or using pure phospholipids. It should be noted that there is a wide variety of phospholipids available for liposome development in cosmetic applications. Key parameters of phospholipids, such as HLB (Hydrophilic-Lipophilic Balance), CPP (Critical Packing Parameter), the charge and nature of its polar group and the length and saturation of its non-polar tail, must be taken into account for the development of an effective product. In addition, the use of other compounds such as stabilisers (cholesterol is the most used) and,depending on the release strategy, other lipids such as ceramides, additives that improve the flexibility of lipo-somes or their penetration into the skin, and compounds that modify surface charge, among others, are highly recommended to achieve the best results. Regarding their morphology, there are several types of structures depending on the lamellarity (number of lipid bilayers), their disposition and the size of the liposome, the most common being the following: Where SUV (Small Unilamellar Vesicles) are small liposomes with a single lipid bilayer, MLV (Multi- Lamellar Vesicles) are multilayered and the most used in cosmetics, LUV (Large Unilamellar Vesicles) are larger monolayer liposomes and MVV (MultiVesicular Vesicles) where we can find smaller liposomes trapped within larger ones.

figure 2: Types of liposomes.figures: Indermal/nanovex Biotechnologies

Selection of composition

The selection of the composition and other parameters related to its morphology (size or lamellarity, among others) depends on the compound to be encapsulated, on the skin layer where this encapsulated compound must be released and on the cosmetic product where liposomes will be dispersed. For example, for a surface delivery, large liposomes (MLV or LUV) are used, containing, in addition to phospholipids and cholesterol, other lipids which contribute to deliver the encapsulated compound on the most superficial layers of the skin. On the other hand, for deeper deliveries, liposomes of a smaller size (MLV or SUV) containing compounds that improve membrane flexibility and penetration enhancers are the most common strategy. Different pictures of liposomes used on deep, surface, hair and follicle delivery are shown in figure 3. The liposomes used in these experiments are marked with a red fluorophore (rhodamine) to track the penetration.

The pictures prove the great specificity of these systems in reaching the target layer/area.

figure 3: Deliveries with specific cosmetic targets. figures: Indermal/nanovex Biotechnologies

Variety of options

Most of kinds of compounds can be encapsulated by liposomes. There are logical limitations, such as the size of the compounds to be encapsulated (compounds larger than liposomes, such as probiotics, cannot be encapsulated). Liposomes can encapsulate both lipophilic compounds (within lipid bilayers) and hydrophilic compounds (in the aqueous spaces in the centre of the liposome or between the bilayers). Furthermore, compounds of different nature can be encapsulated: molecules, peptides, proteins, or extracts, among others. It should be noted that it is possible to encapsulate several of these compounds, even if they are of different nature, in the same liposome.

Amount of encapsulation

The amount to encapsulate is a very important parameter to be considered, since it is closely related to the encapsulation efficiency. Although each case is different, the concentration of the active to be encapsulated should be lower than 50% of the liposome concentration. Exceeding this amount leads to low encapsulation efficiency and, therefore, the majority of the active would be unencapsulated.

Possible uses

Liposomes are stable in aqueous media. This means that they can be added to any formula with an aqueous phase: gels, emulsions, or double emulsions, among others. On the other hand, liposomes should not be added in pure oily media since because of the lipophilic nature, they would dissolve. If liposomes have been developed using the right formulation and manufacturing process, they can resist: