New technologies to allow transdermal delivery of therapeutic proteins and small water-soluble drugs

Drugs currently on the market that can be delivered in patch form tend to be small, moderately lipophilic, potent drug molecules. The horizon of transdermal delivery can be expanded to small water-soluble drugs as well as macromolecules, such as therapeutic proteins, by several enhancement technologies that are being actively investigated. One promising technique is iontophoresis, which has been used for localized delivery of drugs, such as corticosteroids or lidocaine, for several years. Recently, a self-contained pre-filled wearable patch utilising this process has been commercialized for systemic delivery of fentanyl. A glucose-monitoring device based on electro-osmotic flow, which enables extraction of glucose from the interstitial fluid via reverse iontophoresis, is also on the market. Most of the other technologies use physical energy to permeabilize the skin. However, the current used in iontophoresis primarily acts on the drug itself. Delivery is controlled by the current and can thus be modulated if desired. The charge, size, structure, and lipophilicity of the drug all influence its transport. For peptides and proteins, the ideal candidate for iontophoretic delivery is that with a high isoelectric point and a molecular weight <10 kDa. For larger proteins, skin microporation and phonophoresis are promising techniques. Skin microporation can be achieved by thermal means or by using mechanical microneedles. This minimally invasive technique is painless and can deliver a drug of any size through the micron-sized holes created in the skin. Mechanical microneedles may be made of silicon, metal, polymer, or maltose and may be solid or hollow. Phonophoresis or sonophoresis uses sounds that have a frequency beyond 20 kHz to permeabilize the skin. Electroporation is another technology that reversibly permeabilizes the skin by the application of short, high-voltage pulses. Other technologies being evaluated include chemical enhancers, liquid spray-on products, controlled skin abrasion, radiofrequency induced microchannels, and particle mediated immunization.