Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 389

like vasopressin by Choi et al. [4] . The penetration enhancer is a small molecule
whose primary role is enhancing transdermal drug delivery either by loosening tight
junctions of keratinized cells of the stratum corneum or by increasing membrane flu-
idity. Penetration enhancers leach water-soluble constituents from the stratum cor-
neum and increase its fluidity, thereby increasing the rate of penetration.

8.2.1.1 Factors Influencing the Effectiveness of Penetration Enhancers
A plethora of factors affect the efficacy of penetration enhancers, including physico-
chemical properties of the peptide and protein drug, route and site of administration,
nature of the vehicle, and solvent employed, to name a few. These factors are dis-
cussed in depth below.

�.2.1.1.1 Physicochemical Properties of Peptide and Protein Drugs
Physicochemical properties of the candidate protein and peptide molecules play a
crucial role in facilitating the selection of a penetration enhancer. Guy and Hadgraft
[5] investigated percutaneous penetration of drugs with different lipophilicities using
different penetration enhancers. These workers investigated drug diffusion through
the skin by diffusion across the stratum corneum ( Fig. 8.1 ) and viable epidermis with
a partitioning process at their lipophilic-aqueous phase interface. Two model enhanc-
ers are considered here: the first model augmented only the drug diffusion across the
stratum corneum, whereas the second model enhancer not only increased the diffu-
sion coefficient across the stratum corneum, but also reduced the stratum corneum
viable tissue distribution coefficient. Their observation was a major yardstick for
penetration enhancers as it provided insight into which type of penetration enhancer
should be employed. Observations showed that lipophilic drugs would benefit only
from the second type of enhancer, whereas hydrophilic drugs would benefit from any
of the classes of penetration enhancers.

Figure 8.1 Schematic view of
stratum corneum containing
compactly arranged keratinized
horny densely interspersed in
lipoidal matrix.

Lipid matrix
(amphipathic phospholipid molecules)

Horny keratinized cells

Plasma membrane

Filaments