It is possible to achieve a sustained drug flux for 24 h by incorporating the active material into a moist matrix such as
a hydrogel that serves as an infinite reservoir. The matrix holds the drug on the skin in a soluble form, which makes it available
for delivery through the aqueous microchannels. The matrix releases the drug slowly at a rate suitable for delivery, enabling
the drug concentration in the blood to be maintained as long as 24 h. This effect was shown in a human study of granisetron
delivery. The study measured the transdermal delivery of granisetron (a charged, water-soluble molecule) during a period of
24 h. The drug was administered through a small patch (5.6 cm2 ) using a microelectronic system based on RF cell ablation (the ViaDerm system). This delivery method was compared with other
routes, including passive transdermal delivery, oral delivery (one tablet every 12 h), and intravenous (IV) delivery. The
study was conducted on six healthy adult volunteers in each test group. The results (see Figure 8) revealed differences in
the plasma-drug levels and profiles between the treatments. The IV and oral deliveries displayed a peak or peak-and-valley
profile corresponding to the administration regimen. In contrast, the transdermal delivery through microchannels resulted
in a concentration increase up to 9 h and a constant level up to 24 h, indicating that the channels enabled drug delivery
for at least 24 h. The control group (marked as "ViaDerm untreated" in Figure 8) showed very low plasma levels across the
entire time period, emphasizing that the skin pretreatment used to form microchannels enabled the transdermal delivery of
this water-soluble molecule.
The variability in drug levels in the blood of subjects treated with the system using RF cell ablation was similar to that
measured for oral delivery. This finding confirms that RF microchannel formation is uniform and reproducible.
Factors influencing bioavailability and delivered dose
A large delivered dose and high bioavailability are important for any drug-delivery method, particularly for costly macromolecule
active materials. If the bioavailability of the protein using a specific delivery method is low (< 10–20%), there is a significant
loss of protein. Alternative delivery routes for peptides and proteins result in low bioavailability compared with subcutaneous
injection (12). A microelectronic system based on RF cell ablation using printed-protein patches resulted in very high bioavailability
of up to 40% relative to subcutaneous injection. Table II shows the bioavailability of three drug molecules. The data show
that a low (i.e., 6%) or high (up to 40%) relative bioavailability is attainable, depending on the ratio between the amounts of active material
Drug delivery through microchannels
Drug delivery through microchannels using RF cell ablation may be affected by the molecular size of the molecule delivered,
water solubility, concentration, microchannel density, duration of delivery, dosage forms, drug profile, type of patches,
and drug accumulation.
. No data exist regarding the limitation of the size of drug molecules that can penetrate the microchannels. The transdermal
delivery of small-molecule drugs can be increased significantly by pretreatment. In addition, macromolecules such as peptides
and proteins can also be delivered systemically through the skin using this technology.
Solubility in water.
The microchannels are filled with interstitial fluid. Water-soluble molecules, therefore, can be easily delivered through
the microchannels of the inner layers of the skin and by systemic circulation. Water-insoluble drugs can be delivered transdermally
using RF cell ablation by increasing the water solubility through a suitable formulation.
As in any passive delivery, the rate of delivery depends on the concentration gradient. Increasing the drug concentration
on the skin in the vicinity of the microchannels will result in a higher delivery rate.