Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 641

topical delivery of peptide and protein drugs is also significant; one example is the
use of the growth factor for wound healing. Proteins are also given as antigens for
topical delivery for vaccination. Biotechnology products in development for skin dis-
orders include the recombinant proteins onercept and interleukin (IL) 18 bp, the fusion
protein denileukin diftitox, and the monoclonal antibodies eculizumab, adalimumab,
and antiangiogenesis monoclonal antibody [125,126] . For conventional drugs, topical
products to treat dermatological ailments have been in continual use from the outset.
Although transdermal delivery is moderately new, the principles involved are better
understood than for topical delivery. This is mainly because with transdermal delivery
the blood concentration needed to achieve therapeutic effects is recognized. For topical
delivery, the skin is the target organ. In contrast to transdermal delivery, a non-steady-
state transport generally characterizes a topical drug product. An optimal drug buildup
in the skin, with little or no flux through the skin, is desirable, which does not occur
in transdermal delivery. The topical delivery of small molecule drugs has been used to
deliver therapeutics transdermally and transmucosally. Again, because of the size of
the protein, it is often not feasible to deliver enough protein to achieve systemic levels
of the drug. It is possible to deliver protein-based therapeutics locally by a topical for-
mulation [125,127] . Regranex, a platelet-derived growth factor-based topical formula-
tion, has been approved by the FDA for the treatment of diabetic ulcers [128,129] .
12.2.1 Growth Factors
The wound-healing process in the body is always accompanied by the discharge of
a number of protein-based growth factors that assist the healing [130,131] . These
growth factors are now formed biotechnologically in a commercially feasible manner,
therefore increasing the possibility of fast healing of wounds. The use of growth fac-
tors can hasten the healing process after surgery. With respect to health care costs, this
could result in enormous savings. This rationale is driving a number of companies and
other academic and government organizations to develop growth factors. Although
growth factors also have application in ophthalmology, a chief indication for their
use is to accelerate wound healing in the skin. The most promising agent for such
use is the epidermal growth factor (EGF), a polypeptide of 53 amino acid residues,
which has shown of the capability to heal open and burn wounds. It was found that
the existence of protease inhibitors is necessary in the formulation to stabilize EGF
at the wound site [132,133] . Formulations of acidic fibroblast growth factor were also
reported to accelerate wound healing in a diabetic mouse model [133] . In the same
way, transforming growth factor- (TGF-) is used topically to accelerate wound
healing. One patent involves a lyophilized protein formulation containing a cellulose
polymer as a gelling agent. When reconstituted, the formulation forms a gel that can
then be used topically [134] .
12.2.2 Liposomes
The literature on the use of liposomes for topical or transdermal delivery appears to
have reached an accord on the belief that liposomes cannot traverse the skin in intact