How to overcome the limitations of the skin?

The skin is not simply a passive envelope: it is a highly selective barrier perfected over millions of years of evolution.

Its outermost layer, the stratum corneum, is designed to block the entry of most foreign molecules. Only those with a molecular weight below 500 Daltons, optimal lipophilicity, and neutral charge can passively diffuse through it. This natural filter restricts the efficacy of numerous active ingredients, especially peptides, growth factors, and other high-value biological molecules.

The problem of concentration and penetration

A common mistake in formulation is increasing the dose of an active ingredient expecting greater efficacy. Imagine a water-soluble ingredient at 1%: increasing its concentration does not necessarily improve the result, because the skin barrier limits the fraction that manages to cross the stratum corneum. The excess simply does not penetrate.

Encapsulation offers a partial solution to this problem. By enclosing the active ingredient in a suitable vehicle, it is possible to overcome the 500 Dalton restriction. However, this strategy involves an inevitable trade-off: the effective concentration within the vesicle is typically reduced by a factor of ten (from 1% to 0.1%). The gain in penetration — up to ten times greater — compensates for this loss, achieving a net efficacy comparable to that of the free active ingredient. Even so, encapsulation is indispensable when working with molecules that cannot cross the skin barrier on their own.

Adding multiple encapsulated actives to the same formula is not the solution either: encapsulated systems tend to interact, fuse, or degrade, compromising both the stability and safety of the product.

Encapsulation systems: from conventional to advanced

The efficacy of a cosmetic or dermal formulation depends not only on which actives it contains, but on how they reach their site of action. The choice of encapsulation system is just as decisive as the selection of the ingredient itself. Advances in ultra-deformable and dynamic-loading vehicles open new possibilities for formulating products that overcome the structural limitations of the skin, not merely work around them.

Liposomes and Exosomes

• Liposomes are the best-known encapsulation vehicles. They are biocompatible, but present two important limitations: low loading capacity and a tendency to release the active ingredient prematurely before reaching the target tissue.
• Exosomes represent a more sophisticated conceptual evolution. They are cell-derived nanovesicles that transport proteins, lipids, and RNA between cells, offering great potential for targeted active delivery and tissue regeneration. Their efficacy, however, depends greatly on their origin: when not autologous (not derived from the patient themselves), their performance decreases significantly, approaching that of conventional systems.

Transfersomes

Transfersomes represent a qualitative leap in the design of dermal vehicles. Their ultra-flexible structure allows them to deform and adapt to the narrow intercellular spaces of the stratum corneum, reaching layers that rigid vehicles cannot access.

This adaptive capacity translates into an efficacy approximately double that of conventional liposomes, delivering an effective concentration of around 2%.

Genosomes

Genosomes, developed within the TDX20® system, represent the state of the art in active dermal encapsulation. They combine the ultra-deformability of transfersomes with a dynamic and distinctive loading mechanism: subjected to intense mechanical agitation in the XGEN reactor, their vesicular structure opens transiently, allowing them to capture the actives already present in the formulation and reseal with an internal concentration up to twenty times higher than the external medium.

The result is a vehicle that not only penetrates effectively into deep layers of the skin, but carries a far superior active payload compared to any conventional system, without compromising formulation stability.