Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 626

of skin exposed to the current, the duration of applied current, and the module of
applied current. It permits fast and easy cessation of drug delivery in case of emer-
gency. Iontophoresis improves the delivery of high-molecular-weight compounds as
well as polar molecules. Iontophoresis is safe as it allows restoration of the skin bar-
rier function without producing severe skin irritation and has the ability to be used
for systemic delivery as well as local (topical) delivery of drugs.
Factors Affecting Iontophoretic Delivery
Molecular Weight and Size Molecular weight and size is the most significant factor
affecting iontophoretic drug delivery.
Figure 12.4 shows the effect of molecular size on the relative importance of elec-
trorepulsion (ER) and EO to the overall iontophoretic transport of ions.
Small, highly mobile cations are principally moved across the skin by ER. But
with an increase in molecular size, the fraction of charge carried by a cationic drug
decreases, and the principal mechanism of transport becomes EO. As molecular size
increases for cations, there will therefore be a transition in the dominant mechanism
from ER to EO [35] . For anions, EO is a negative contribution to the total flux, and
once the molecular size reaches a critical value, it completely cancels out the ER con-
tribution to electrotransport (resulting in no net flux). Highly mobile ions (e.g., Na  ,
Cl - , and small charged amino acids) are principally moved across the skin by ER,
whereas large, bulky species carrying only a part of the charge passing across the skin
can only be transported by EO. As molecular size increases for cations, there will
be a transition in the dominant mechanism from ER to EO. For anions, on the other

ER EO Total

Anionic drug Cationic drug

0 0

Molecular size Molecular size

m c

Figure 12.4 Effect of molecular size on the relative importance of ER and EO to the overall
iontophoretic transport of ions.