Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 642

form due to their structure. Consequently, they will usually not improve percutaneous
absorption of entrapped drugs, although they are likely to augment topical delivery
into epidermis and perhaps to dermis as well [135-138] . It has been suggested that
liposomes, being lipophilic, may enter the lipid-rich external skin layers and then
are localized because of the hydrophilic environment of the dermis. Nevertheless, it
may be difficult to ascertain how relatively large lipid vesicles cross densely packed
epidermal tissue to reach within the intact dermal layers; the mechanism involved
is not apparent. Analytical techniques must be developed that can distinguish skin
and liposomes [137] . The reason for reduced epidermal and dermal clearance of
liposome-entrapped drugs is recognized as being due to the unavailability of the
metabolizing enzymes within the skin to the encapsulated drug. It has also been sug-
gested that larger liposomes, unable to penetrate the underlying blood vessels, act as
localized sustained release vesicles [139] . Additionally, liposomes improve solubil-
ity of poorly soluble drugs, and their phospholipid constituents may act as penetra-
tion enhancers to facilitate topical absorption [138] . Lecithin is commonly used in
pharmaceutical, cosmetic, and food products and has GRAS status. Lipids as such
and liposomes have been incorporated into many cosmetic formulations [140,141] .
Unlike liposome-, lipid-containing preparations have been marketed as cosmetics.
The liposomes-containing products in the market include the antifungal drugs econ-
azole (Pevaryl®, Cilag, AG) and amphotericin B. Unlike water-soluble peptide and
protein drugs, which are entrapped in the aqueous environment within the liposome,
drugs that are associated with the lipid bilayer use liposomes for topical delivery. The
method of liposomal preparation is the most important factor determining the effec-
tiveness of the formulation. The dehydration-rehydration method was most effective,
presumably because dehydration and subsequent rehydration of the liposomes facili-
tates partitioning of the interferon into liposomal bilayers [142] . In continuing stud-
ies using an in vitro diffusion setup, it was observed that liposomes made from “skin
lipids” were twice as effective as those made from phospholipids, perhaps because
they are better able to transfer the drug to the skin [142] . Unlike other biological
membranes, the SC does not contain phospholipids and is made primarily of cerami-
des, cholesterol, fatty acids, and cholesteryl sulfate.
12.2.3 Iontophoresis and Phonophoresis
Although investigations of the potential use of iontophoresis and phonophoresis tech-
niques to achieve systemic delivery of drugs are relatively new, having only begun
over the last one or two decades, these techniques have been used for topical delivery
of drugs and in physical therapy for several years. The technique of iontophoresis is
used routinely in clinics by physical therapists for the delivery of corticosteroids and
local anesthetics to treat inflammatory conditions of muscles and tendons, such as
tendonitis, bursitis, carpal tunnel syndrome, arthritis, temporomandibular joint dys-
function, and others. Several devices and electrodes are commercially available for
this purpose, and the most commonly used drug for iontophoretic delivery is dexa-
methasone sodium phosphate. Similarly, phonophoresis is also routinely used in clin-
ics by physical therapists, with hydrocortisone a commonly administered drug [143] .