Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 640

delivery eightfold at pH 7.4 [120] . Sodium glycocholate, a penetration enhancer, may
also act as a protease inhibitor. A dual role may be played by a variety of mechanisms,
such as by tightly binding to or covalent modification of the active sites of proteases
or by chelating metal ions essential for proteolytic activity.
12.1.4.3 Other Technologies
Delivery of peptides and proteins across the skin is carried out by physically circum-
venting the SC barrier in ways designed to be less invasive than the use of a classic
injection. Among the approaches used are ablation of the SC by laser radiation, heat, or
erosion, and particle bombardment. All these approaches can be used in combination
with electrical methods [121] . The mechanism by which this laser beam disrupts the SC
is complex, yet quite reproducible and controllable, in that the number of laser pulses
is correlated to the degree of SC damage. Lasers are physical devices that have been
used for medical diagnosis and therapeutic purposes. The erbium:yttrium-aluminum-
garnet (Er:YAG) laser, a tool used to provide overall skin rejuvenation, from simple
lentigines to deeper rhytides, causes minimal residual thermal damage [122] . The dura-
tion of the skin's exposure to the laser is in the range of nano- to microseconds. To
obtain pure photomechanical waves (PWs) generated by the laser and exclude the SC
ablation effect, a polystyrene lens is used to filter the laser light for comparison. The
Micro Pors TM technology consists of directing tightly focused thermal energy into the
SC to create micropores. The skin is contacted by a wire mesh through which a current
is passed, causing local heating sufficient to create small holes in the barrier. Delivery
of insulin by this approach has been tried [122] . A more macroscopic method to cre-
ate an erosion in the SC is via suction deepithelialization [123] . Using a vacuum, a
small blister (6 mm diameter) is formed on the skin; the tissue separates at the dermal-
epidermal junction. The roof of the blister is then removed, or “guillotined,” expos-
ing a small area of dermis to which a drug solution is directly applied. The dermal
microcirculation remains intact and functional following creation of the erosion. Mild
inflammation is observed and the erosion self-heals over time with, apparently, mini-
mal scarring. But practical applications of this approach, especially for chronic disease
treatment, look unlikely, and issues related to local infections must be addressed. High-
velocity particle delivery across the skin is the technology of a major drug-delivery
operation designated in the UK and the USA (PowderJect Inc.) [124] . Once a drug has
been formulated as an appropriate and well-characterized powder, it is then introduced
into a compact handheld device in which a supersonic flow of gas accelerates the par-
ticles to a speed high enough that they collide with the skin, creating enough energy to
penetrate the skin's outer layers and effect drug delivery. The depth and extent of deliv-
ery depends on the speed, diameter, and density of the drug particles.
12.2 Topical Delivery of Proteins and Peptides
A great deal of research for delivery of peptide drugs is currently centered on trans-
dermal delivery, that is, percutaneous absorption for systemic results. Nevertheless,