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.
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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
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