Mentor  Pharmaceutical Consulting


 
 
 

Transdermal Delivery of Proteins

The majority of peptide and protein pharmaceuticals are currently administered via sub-cutaneous injection, often requiring considerable patient education, pain and discomfort, and sometimes leading to undesirable side-effects. In contrast, the oral route of administration of peptides and proteins (also available through Mentor) is a much more attractive means of delivery due to the ease of administration, increased patient comfort and is seen as more socially acceptable, thus leading to increased patient compliance and ultimately more effective disease treatment. There are, however many instances where topical or transdermal delivery of proteins would result in much treatments outcomes to patients. Topical administration of various peptides, proteins or other water soluble molecules would have direct application in cases of psoriasis, eczema, topical allergies, skin rashes etc, where it would be much better to apply the pharmaceutical to the site of the disease, rather than to inject the pharmaceutical and "trust" that it eventually with reach the target organ. In other cases, such as for topical vaccination, topical delivery of vaccines would be much more beneficial as it would directly stimulate the antigen presenting cells (the dendritic cells) in the skin rather than in the case of vaccine injection where the vaccine is administered under the skin and thus the vaccine id delivered to a less favourable site.

Transdermal Delivery Devices

Considerable work by many companies and researchers has concentrated on the use of "high tech" transdermal delivery devices, including microneedles, iontophoretic devices, etc, in order to drive peptides and proteins through the skin. These devices all suffer from problems in manufacturing, scalability, ease of administration, and applicability to delivery to large areas of the skin. For these reasons it is very hard for the average research group to access and use these technologies at both the lab scale and in pre-clinical stage.

In contrast water-in-oil microemulsions (W/O ME) have been found to offer significant advantages for delivery of peptides and proteins. Advantages include, but are not limited to:

  • Ease of manufacture

  • Low cost

  • Ease of administration

  • Delivery of milligram quantities of peptides and proteins into the skin

  • Controlled release of peptides and proteins

  • Ability to co-deliver both oil and water soluble molecules

  • Lack of local skin reactions

A number of formulations have been identified that are suitable for topical applications and transdermal delivery of proteins, antigens, adjuvants, LHRH analogues, IGF1, hGH, EGF, anti-inflammatory molecules, antibodies, IgG-Fc-fusion proteins, vitamin B12 and many others. Topical administration of these formulations have found application in weight loss, topical vaccines, topical anti-inflammatory applications, topical delivery of LHRH agonists and LHRH antagonists, amongst others.

Penetration of protein into Sebaceous area*

Penetration of protein into human skin*

Dermal diffusion of topically applied protein to human skin*

Mentor can provide technical advice on

  • The identification of appropriate formulations for topical delivery.

  • Suggestions on methods of formulating different proteins, antigens, adjuvants, etc  for topical application.

  • The selection of appropriate adjuvants for topical vaccines.

  • Appropriate in vivo models.

* Presented at CRS satellite meeting 2007 Salt Lake City