Transdermal delivery of proteins

Abstract

Transdermal delivery of peptides and proteins avoids the disadvantages associated with the invasive parenteral route of administration and other alternative routes such as the pulmonary and nasal routes. Since proteins have a large size and are hydrophilic in nature, they cannot permeate passively across the skin due to the stratum corneum which allows the transport of only small lipophilic drug molecules. Enhancement techniques such as chemical enhancers, iontophoresis, microneedles, electroporation, sonophoresis, thermal ablation, laser ablation, radiofrequency ablation and noninvasive jet injectors aid in the delivery of proteins by overcoming the skin barrier in different ways. In this review, these enhancement techniques that can enable the transdermal delivery of proteins are discussed, including a discussion of mechanisms, sterility requirements, and commercial development of products. Combination of enhancement techniques may result in a synergistic effect allowing increased protein delivery and these are also discussed.

Fig. 1

Schematic of principle behind iontophoresis. Charged drug molecules are propelled into the skin due to the electrorepulsive forces from electrodes of similar polarity

Fig. 2

Different application modes of microneedle technology. a Poration of the skin with solid microneedles followed by application of drug-loaded patch; b insertion of drug-coated solid microneedles; c insertion of drug-encapsulated soluble microneedles; and d insertion of hollow microneedles for infusion of liquid formulations

Fig. 3

Schematic showing the principles of a electroporation, b thermal ablation, c sonophoresis, and d laser ablation. a Electroporation: application of high voltage alters the permeability of the skin and enhances drug delivery; b thermal ablation: an electric pulse is converted to thermal energy on the microfilaments, thereby causing localized high temperature on the stratum corneum surface which vaporizes a localized region to create a micropore; c sonophoresis: activation of the probe transmits low-frequency waves which alter the permeability of the skin by cavitation and local heating; d laser ablation: activation of the probe transmits a laser beam which heats the skin surface causing the water molecules to evaporate rapidly thereby creating microchannels in the epidermis