Advances in Radio-Frequency Transdermal Drug Delivery
A microelectronic system based on radio-frequency (RF) cell ablation addresses limitations of other transdermal drug-delivery methods. This system expands the transdermal spectrum to include the delivery of water-soluble molecules, peptides, proteins, and other macromolecules.
The skin's low permeability limits the types of drugs that can be delivered transdermally. Many drugs with a hydrophilic character
permeate the intact skin too slowly to be of therapeutic benefit (10). Under RF cell ablation, pretreating the skin allows
aquatic channels to form across the stratum corneum, which provides significant enhancement in the permeability of water-soluble
compounds. Drugs that exhibit insufficient solubility in water can still benefit from the technology. By increasing solubility
using various formulation approaches, such as drug-cyclodextrin complexes or dissolving the drug in a water-alcohol mixture,
the drugs are also able to permeate the skin. Table I shows the in vitro skin permeability of various drugs in a dynamic diffusion-cell model using full-thickness porcine skin. The results show
enhanced transdermal delivery with the hydrophilic compounds—granisetron hydrogen chloride (HCl) and lidocaine HCl. Lidocaine
HCl is more water-soluble than diclofenac sodium and had higher delivery rates. The effect of the compound concentration on
its delivery rate was shown with testosterone (2% versus 6% in aqueous solution) and lidocaine HCl (2% versus 5% in aqueous
solution). The delivery rate increased linearly with the concentration of the loaded compound.
Effect of molecular size on delivery rate
The effect of molecular size on the delivery rate of macromolecules through the treated skin was shown in a study using fluorescein
isothiocyanate-labeled dextran molecules of various sizes: 10, 40 or 70 kDa. This in vitro experiment tested the delivery of these macromolecules through a full-thickness porcine skin that had been pretreated with
the device. An increase in molecular size brought about a decrease in delivery rate (see Figure 6). However, it is important
to note that even the largest 70-kDa molecule was successfully delivered transdermally through the RF microchannels.
Effect of patch technology on pharmacokinetic profiles
Based on the patch technology used, two types of drug profiles are feasible using the microelectronic system (ViaDerm). When
a patch based on a dry formulation is used (i.e, a protein-printed patch), a peak-drug profile is observed in the blood, which resembles a profile of a subcutaneous injection.
Figure 7 shows the blood profile for delivering human growth hormone in pigs. The peak Cmax (maximum concentration) is affected by the patch dose (see Figure 7a) or by microchannel density (see Figure 7b). Figure
7a shows that increasing the drug load on the patch resulted in a higher delivered amount. Figure 7b shows the effect of microchannel
density on the efficiency of drug delivery. Increasing the microchannel density from 150 to 300 microchannels (MCs)/cm2 resulted in a much higher delivered amount without increasing the drug load on the patch. This technique also significantly
increased the bioavailability of the drug.