Product Opportunities
Significance
of Drug Delivery
Transdermal
Transport Systems (TTS)
Targeted Drug Delivery Through
the Skin
IDEA'
s Product Portfolio
Patents
Significance of Drug Delivery
Pharmaceutical companies are realising more and more that the return
on investment for the improved delivery of approved (marketed) compounds
is typically greater than the return on developing related new chemical
entities. Many major corporations have also found that from thousands
of product candidates only those agents which are "packaged" and
delivered properly into the body will flourish on the market. This is
accomplished by drug delivery groups which, more often than not, reside
outside the big-pharma companies.
Transdermal Transport Systems (TTS)
Conventional TTS that deliver drugs to the whole body have been known
and used for decades. They constitute a worldwide annual market in excess
2 billion dollars; if one includes analgesic patches for regional therapy,
the market exceeds 3 billion US dollars.
 |
Effect of molecular weight
and lipophilicity on the rate of transdermal transport in case of
permeation (upper and lower green curve for the more or less lipophilic
substances, respectively) or of the Transfersome® mediated penetration
(blue line and bullets). Green bullets represent the commercial drugs
in transdermal patches (click to
enlarge). |
Historically, the main reason for the success of transdermal delivery
was the avoidance of first-pass metabolism. This increases drug bioavailability
in comparison to oral formulations. Transdermal formulations also deliver
drugs with a steady rate (first order kinetics), which is an additional
advantage. However, transdermal drug delivery methods have their drawbacks.
Most important are the unwanted local side effects (skin irritation/toxicity)
and the fact that conventional TTS technology is only suited for delivering
relatively small drugs across the skin. The green symbols in the figure
above define all important drugs in TTS devices that are used to date.
New transdermal drug delivery methods are therefore required to drive
future growth in transdermal product markets. Biological products would
also profit greatly from new, non-invasive delivery. The original players
in the transdermal field failed to introduce such improvements, which
were then introduced by a number of innovator companies, including .
Broadly speaking, two different new approaches for transdermal drug delivery
are currently being pursued:
- nanoporation/minimum abrasion;
- nanocarriers.
Sonoporation, thermoporation or use of very fine and short needles belong
to the former; ultradeformable carriers (Transfersome® vesicles or,
their typically less advanced kin, such as Ethosomes® or fluid liposomes)
exemplify the latter. Any of these can deliver small or large molecules
across the skin, but only Transfersome® carriers can provide control
over local drug deposition as well.
Targeted Drug Delivery Through the Skin
The therapeutics applied to the skin in a conventional fashion, e.g.
using gel or a patch, all rely on the drug’s concentration gradient
(chemical “force”) to drive molecular diffusion through the
stratum corneum. A drug molecule that has overcome this primary skin barrier
continues to diffuse below the stratum corneum driven by the same, but
unavoidably smaller force. A drug molecule that has crossed the deeper
skin layers may ultimately reach subcutaneous tissues, such as fat deposits
and muscles. However, to do so the drug molecule must also avoid the skin
microvessels, which form an extensive secondary skin barrier. The free
drug concentration thus declines very steeply from the skin surface towards
deep subcutaneous tissue.
A drug must be prevented from entering into cutaneous blood vessels to
overcome the problem of its local clearance. Until recently, this could
only be done by injecting a suitable drug depot formulation below the
skin. With ’s
products designed for targeted drug deposition into peripheral tissue
the same goal is achieved by using Transfersome® carriers. The latter
are water—rather than drug—concentration driven and deformable
enough to overcome the primary skin barrier and too large to be taken-up
by cutaneous blood microvasculature; Transfersome®-drug association
then also precludes rapid drug dissipation. Such carriers consequently
promote drug accumulation and retention at the chosen subcutaneous site,
by way of controlled vesicle deposition at such a site and prolongation
of the duration of drug-carrier association. This is a major—and
therapeutically much needed—advantage of Transfersome® mediated
drug transport into target peripheral tissue, unmatched by any conventional
drug delivery method.
The depth and extent of the carrier-mediated drug deposition is chiefly
controlled by the applied Transfersome® dose per area, and not by
the total drug amount used, owing to the fact that the carrier transport
across the skin is osmotically rather than chemically driven. This unmatched
feature of Transfersome® technology is highlighted in the table below:
’s
technology is therefore ideally suited for controlling the depth and rate
of drug delivery, and for improving drug accumulation in deep subcutaneous
tissues, such as muscles and joints below the local application site,
whilst minimising systemic drug exposure.
IDEA's Product Portfolio
's
non-invasive drug delivery system, the proprietary Transfersome®
carriers, is the method of choice for administering various therapeutic
agents into and across the skin barrier in a controlled fashion. The concept
has been proven in vivo for a number of drugs in Transfersome®
formulation prototypes.

's
long term focus is the development of novel dermatological products. Currently,
the Company is using Transfersome® cariers to transport the established
low molecular weight drugs selectively into the skin and, in particular,
the underlying deep tissues. Such regional delivery generally can be safer,
more convenient, and more efficient than conventional topical applications.
Furthermore, Transfersome®-mediated drug delivery can provide good
control over the depth of deposition of the active ingredient and/or kinetics
of drug release.
The Company is pursuing the commercial opportunities of several such
products listed in the table above.
The Targeted Analgesic IDEA-033
Dermatics
- Topical drug delivery into the skin
Regio-selective therapeutics
- Delivery to deep skin and underlying muscles/joints
Systemic therapeutics
- Delivery to the whole body
Patents
holds close to 60 issued patents from 9 international (PCT)
patent families for the Transfersome® technology and its transdermal,
transnasal applications, incl. vaccination, in the major pharmaceutical
markets. These patents cover the composition of matter, methods
of use, carrier manufacturing, loading with drugs, and other relevant
technological aspects.
|