Mentor  Pharmaceutical Consulting


 
 
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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, alternative routes of administration of peptides and proteins are potentially much more attractive as a means of delivery due to the ease of administration, increased patient comfort and may be seen as more socially acceptable, thus leading to increased patient compliance and ultimately more effective disease treatments. There are many instances where topical or transdermal delivery of proteins would result in much better treatment outcomes for patients. For instance in conditions such as psoriasis, eczema, topical allergies, skin rashes etc, 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 reaches the target organ. In other cases, such as vaccination, transdermal delivery has the added benefit of being able to directly stimulate the antigen presenting cells (the dendritic cells) in the skin rather than sub-cutaneous injection or intramuscular injection where the  vaccine is 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. This has formed the basis of the development of Transdermal Protein Technology (TPT). Advantages of TPT 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

Using TPT various formulations have been developed that are suitable for topical applications and transdermal delivery of proteins, antigens, adjuvants, LHRH analogues, IGF1, hGH, EGF, anti-inflammatory molecules, antibodies, Fc-fusion proteins, and many others. Topical application of these formulations has found application in weight loss, vaccination, administration of anti-inflammatory formulations, delivery of LHRH agonists and LHRH antagonists, amongst many others. Additionally TPT has been used to develop a formulation that has potential application in the treatment of multiple sclerosis, Parkinson's disease, arthritis, Crohn's disease, psoriasis, eczema, ulcerative colitis.

Penetration of protein into Sebaceous area*

Penetration of protein into human skin*

Dermal diffusion of topically applied protein to human skin*

Topical/transdermal Delivery of Insulin

Topical application of insulin using transdermal delivery system results in insulin forming a slow releasing depot within the skin. The sustained release of insulin into the circulation is slow enough to prevent a reduction in serum glucose, however, it is able to cause weight loss and an increase in muscle mass concomitant with the anabolic activity of molecules such as insulin, IGF1 and hGH.

Topical/transdermal Delivery of antibodies such as Humira/Remicade/Enbrel

The skin penetrating activity of water-in-oil microemulsions is highly suited to the topical delivery of large water soluble molecules such as antibodies, antibody fragments and antibody-Fc fusion molecules. Topical application of the transdermal delivery system incorporating Humira, Remicade, or Enbrel has shown efficacy in reducing joint inflammation in the carrageenan model of arthritis.

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.

Mentor can provide pre-formulated oils suitable for topical delivery of proteins

* Presented at CRS satellite meeting 2007 Salt Lake City

Himes R., Lee S., McMenigall K., Russell-Jones G.J. (2010). Reduction in inflammation in the footpad of carrageenan treated mice following the topical administration of anti-TNF molecules formulated in a micro-emulsion. J Control Release 145:3, 210-213.

 Russell-Jones, G. J. and Himes, R. (2011) Water-in-oil Microemulsions for Effective Transdermal Delivery of Proteins. Expert Opin Drug Deliv. 2011 Apr;8(4):537-46.

Himes S.R. Lee S., McMenigall K., Russell-Jones G.J.. The influence of molecular adjuvants in the cutaneous response to antigen after topical vaccination. Vaccine Jul 26;29(33):5393-8