Dendrimersomes for Ingredient Delivery

In recent years, encapsulation to deliver cosmetic ingredients into the skin has boomed. However, to deliver an ingredient into the epidermis, the vehicle must mimic biological cell membranes that comprise phospholipids, carbohydrates, cholesterol, proteins, etc. Therefore, interest has grown in structures that mimic the cell membrane. In addition, those that monodisperse and can be triggered to release their contents under various conditions improve delivery as well as formulation flexibility.

Thus far, polymersomes and liposomes have been introduced—vesicles capable of delivering drugs and cosmetic actives into the skin. However, they challenge chemists and formulators in terms of stability, dispersion and methodology. According to Virgil Percec, PhD, a professor at the University of Pennsylvania, dendrimers are the answer to the stable, effective delivery of drugs and cosmetic actives to the skin. Percec’s team has researched the fundamentals of dendrimers for years but more recently published work on using dendrimers to deliver drugs, cosmetic ingredients and other materials to the skin.

Comparing Delivery Vesicles
Vesicles that mimic the biological cell membrane often are generated by a complicated methodology, according to Percec, since each drug release application requires a particular vesicle size. He went on to describe the challenges of delivering materials using liposomes and polymersomes. While polymersomes are stable in solutions when assembled into vesicles, according to Percec, they pose dispersion problems. “Polymersomes polydisperse and require tedious fractionation in order to get monodispersion for specific applications,” said Percec. He added that most polymers are not biocompatible.

Similar to polymersomes, liposomes must be fractionated; however, they are not as stable as polymersomes or they are stable for a shorter period of time. “People have come up with methods to stabilize them, but they are not straight forward,” added Percec.

Percec’s team therefore sought to create a vesicle that mimicked the biological cell membrane but solved the problems of stability, dispersion and the methodological challenges associated with other vesicles. The team sourced dendrimers for this task—specifically Janus dendrimers, and using the nomenclature that preceded them, they termed these vesicles dendrimersomes.

Dendrimers are polymers having every monomer unit branched. They have three main components: a center core, a dendritic or branched interior, and exterior end groups. They are perfectly branched, and have a highly functional surface and an open core.1

In Roman mythology, Janus was the god of gates and doorways and was depicted as having two different faces. Similarly, Janus dendrimers contain two completely dissimilar structures: hydrophilic and hydrophobic dendrons, which together create amphiphilic Janus dendrimers in morphologies such as tubular vesicles, helical ribbons and cubosomes. “We made a water-soluble/water-insoluble molecule—an amphiphilic molecule that behaves like an amphiphilic block polymer or an amphiphilic phospholipid,” said Percec. This dendrimersome self-assembles vesicles in combination with water.

Like the other vesicles, two different materials or drugs can be incorporated into a dendrimersome. However, a dendrimersome can go one step further. “In a vesicle, you can incorporate two different drugs: one that is water-soluble, which goes into the middle of the molecule, and one that is water-insoluble [i.e., hydrophobic], which you incorporate [within the vesicle but around the outside of the water-soluble drug].” In addition to two materials, Percec noted that a third, fourth or fifth one may be added by functionalizing the periphery of the Janus dendrimer. More than two raw materials or actives cannot be easily incorporated into a liposome or polymersome, according to Percec, since they only have one chain end. He explained, “Janus dendrimers have up to 10–20 chain ends in each molecule and by functionalizing them, we do not change their self-assembly behavior.”

Cosmetic Effects
Dendrimersomes can impact cosmetics in that, according to Percec, besides their benefits in dispersion, biocompatibility and stability, dendrimersomes can be offered in a number of morphologies depending upon application. In addition, the methods used to produce these morphologies are reportedly simple, inexpensive chemistries. Percec further adds that dendrimersomes may allow formulators to incorporate a number of raw materials into a formulation.

“In addition to one or two ingredients, [the formulator] may want to functionalize or incorporate dyes on the periphery to provide a color to cosmetics,” said Percec. The research team has not yet examined dendrimersomes in cosmetic formulas, but it has plans to do so soon. Although there is still some research yet to be completed and regulatory approvals to obtain, Percec is optimistic that the technology will be commercially available soon.

1. L Plonsker, Dendrimers that Deliver, Cosm & Toil 119(9) (2004)

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