Advances in recombinant DNA technology and protein-based therapeutics have affected several medical conditions, including diabetes, osteoporosis and cancer. There are multiple protein-drug products for these conditions that are often large polar complex macromolecules with side chains.

This in turn, introduces stability issues and makes their delivery a difficult task to achieve. Therefore, the current routine route of administration is parenteral delivery, which is invasive and entails a historical low patient compliance.

Drug delivery has become an art — providing satisfactory therapeutic effects while introducing minimal side effects. Patient compliance is yet another player in this important task.

This becomes even more cumbersome in cases of poor solubility, large molecular weight or instability of drugs where conventional oral delivery is not applicable due to GI tract degradation. With a large surface area, the skin has been considered as an attractive, cost-effective route of delivery into the systemic circulation.

The transdermal route of administration is not invasive, but passive transdermal delivery is only restricted to small lipophilic molecules, which might not be applicable to hydrophilic or macromolecular drugs.

Back in 1999, a group of researchers successfully performed transdermal delivery of an analog of thyrotropin releasing hormone, which increased almost twofold in the presence of ethanol and cineole. Furthermore, certain peptide sequences have been co-administered in order to increase peptide delivery.

As an example, co-administration of a short synthetic peptide has been reported to increase the passive delivery of insulin human growth hormone through transfollicular route. Another group reported the incorporation of a short peptide into a recombinant melanoma protein targeted for vaccination, which achieved a high titer of the antibody.

Chemical modification has also been tried in order to enhance delivery of therapeutics. For example, a better skin permeability has been reported for lipophilic derivatives. Another approach that has been tried with liposomes, niosoms, ethosomes and transfersomes was peptide encapsulation to increase skin delivery.

The transdermal delivery of peptides can be enhanced with incorporation of penetration enhancers, addition of facilitating peptide sequences, chemical modification of the peptide and encapsulation, but they are only applicable to a proportion of small proteins. In order to address these issues, several different disciplines have got together in order to generate novel engineered delivery routes to increase the scope of mucosal and transdermal delivery.

There have been recent novel technological advances in transdermal delivery techniques — microportaion, iontophoresis, sonophoresis, phonophoresis, chemical enhancers, thermal and radiofrequency ablation, jet injectors, electroporation, microneedles and laser-assisted delivery — that have introduced new hope for the delivery of many therapeutic molecules, biopharmaceuticals, cosmoceuticals and vaccines.

The field of transdermal route protein delivery of therapeutics is very active, with a number of emerging novel technologies that could enhance the skin delivery of hydrophilic macromolecules produced as a result of ongoing advances in recombinant DNA technology and protein-based therapeutics.

Some of these products are commercially available in the market, but a large number of products are still in clinical trials.