Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 633

erythema. Iontophoresis will be contraindicated for patients sensitive to the current
levels used and to patients carrying electrically sensitive devices such as cardiac
pacemakers. Based on differential scanning calorimetry (DSC) and attenuated total
reflection-Fourier transform infrared (ATR-FTIR) studies, it has emerged that the
effects of electrical treatment are less disruptive to the SC compared to the effects
of penetration enhancers [78] . At present, several drug-delivery companies are in the
process of developing prefilled wearable, battery-powered patches for clinical trials
and eventual market launch.
Electroporation in Combination with Iontophoresis Iontophoresis and electropor-
ation are both methods of electrically assisted transdermal drug delivery. Figure 12.5
shows drug penetration pathway in low-voltage iontophoresis and high-voltage elec-
troporation. Iontophoresis is more usually used to deliver hydrophobic low-molecu-
lar-weight drugs, whereas electroporation appears more effective for the delivery of
some macromolecules such as antisense oligonucleotides, peptides, and proteins.
Drug delivery with iontophoresis and electroporation are thought to utilize different
penetration pathways ( Fig. 12.5 ). Electroporation has the advantages of delivery of
macromolecules, quick drug effect onset, and resultant insignificant or minor skin
damage. There is also evidence showing greater drug uptake by skin cells during elec-
troporation. A combination of iontophoresis and electroporation could possibly further
enhance drug transport and allow rapid delivery of a bolus dose and precise control of
drug-delivery rate and programmability. Electrically assisted delivery of sCT (MW
3600) was conducted by Chang et al. [12] . Electroporation pulses (six pulses of 120V,
10 ms each) followed by iontophoresis (0.5 mA/cm 2 ) gave a flux about 4 times higher
than with iontophoresis alone. Lag time of the iontophoretic delivery was shortened
significantly as well. However, pulsing at lower voltages (60 and 100V) followed
by iontophoresis did not result in sCT transport increase over iontophoresis alone.
Pulsatile transdermal delivery of LHRH using electroporation followed by iontopho-
resis was studied [79] . The application of a single pulse (500V, 5 ms as exponential)
to initiate the experiment resulted in a nearly twofold increase in LHRH concentration

Transappendageal
(low-voltage iontophoresis) New pathways

(high-voltage)

Hair follicle

Sweat gland

Figure 12.5 Drug penetration pathways in low-voltage iontophoresis and high-voltage
electroporation.