Delivery is everything -- just ask a stand up comedian. What's true in comedy clubs, is also the case for pharmaceuticals. While no one would debate the importance of drug development and manufacturing, optimal routes of delivery are also an active area of investigation. In fact, the drug delivery market has been rapidly expanding and has become its own market independent of creating new drug compounds.

While nanoscale drug delivery has received a lot of attention for its ability to target specific tissues, delivering drugs through the skin offers an appealing alternative to oral and hypodermic injections. Transdermal drug delivery is easily self-administered, does not require frequent dosing, provides steady delivery and can reduce adverse effects through bypassing liver metabolism.

Although the first transdermal patch was approved in 1979 and the number of new transdermal drugs is steadily rising, the type of drugs amenable to this route of administration remains limited. When thinking of transdermal patches, I think of nicotine and birth control patches. Why do these drugs work transdermally, but others do not? Well, certain compounds can pass through the skin without added help, but most can't. To avoid invading pathogens, our skin provides a first line barrier -- it's outer most layer, the watertight stratum corneum. To get through the stratum corneum, a drug needs to diffuse through intercellular lipids along a path that winds through interlocking cells. This transport pathway limits the types of molecules that can pass though. Compounds that work well for unaided transdermal delivery must be lipophilic with low molecular weights. Additionally, these compounds need to be effective at low doses. As long as a drug fits these standards, transdermal delivery is feasible.

But what about compounds that don’t fit these standard requirements, such as large water-loving compounds? These compounds have generally been limited in their ability to permeate the skin, prompting investigation of how to get them across. One way this has been done is through the addition of non-active chemicals that make the skin more permeable. For example, compounds increasing penetration of the skin have been added to migraine medicine. In general, these transdermal 'enhancers' attempt to reversibly disrupt the stratum corneum to increase permeability and provide a driving force for transport. Ideally, this would also be done without damaging the lower layers of the skin, but these compounds often struggle to balance the opening of the stratum corneum without damaging the lower layers of skin.

Recently, researchers at Korolinska Institute investigated the molecular structure and function of the stratum corneum through a novel method of freezing skin samples. They were able to create a detailed model of the molecular structure of the stratum corneum, which had not previously been done. This enhanced understanding of skin function could improve transdermal delivery and, using the findings from this study, the researchers hope to model drug permeability. "We can now construct computer simulations to help us find out which substances have to be added to different drugs to open up the skin," said Lars Norlén, the leader of the study. "We hope to one day be able to administer regular drugs like insulin and antibiotics this way."

The ability to molecularly open the skin is less invasive then other current methods to increase skin permeability, such as microneedles and ablation of the stratum corneum. Furthermore, this method could also potentially be used for vaccine administration. Transdermal vaccinations could vastly improve third world health care through the reduction in medical waste and disease transmission via the reuse of hypodermic needles. Just one more way that delivering drugs through the skin could improve health care.