Proteins passive transdermal delivery

The skin offers an even less naturally permeable boundary to macromolecules than the gastrointestinal tract. Thus, passive transdermal delivery of proteins and peptides using patch technology has not succeeded. Peptides and proteins can be shot through the skin into the body using high-pressure needle-less injection devices. The devices, which inject proteins like insulin, have been available for years, however they have failed to impress doctors or patients due to the associated discomfort and the potential for splash back to transmit blood-borne diseases such as AIDS or hepatitis. 

It is widely accepted that the two most important physicochemical parameters that determine a molecule s skin permeability are a) its lipophilicity, with a log (octanol/water partition coefficient) value of 2 being quite favorable, and b) its molecular size— smaller compounds permeating better than big ones. " Thus, it is no surprise that the passive transdermal delivery of peptides and proteins, which are typically either very polar (or charged) and/or of high molecular weight (>1000 Da), is extremely inefficient and rarely results in fluxes, which would elicit significant therapeutic effect. 

The remarkable resistance of the SC intercellular lipid network to the passive penetration of therapeutic agents has intensified the search for devices, chemical and physical, with the ability to perturb this lipid environment. Of the many physical techniques investigated, iontophoresis (or electrically enhanced transdermal transport) has become an important focal point [160-162]. Unparalleled in its ability to deliver (noninvasively) ionized drugs across the skin, its modus operandi appears to be largely dependent on transcutaneous ion-conducting pathways (which may be paracellular), rather than a function of direct interaction with the lipid infrastructure [163]. Nevertheless, the effect of the applied current on the lipid (and protein) domains is a matter of interest with respect to both safety considerations (i.e., does the applied current induce stmctural alterations ) and mechanistic insight. ATR-FTIR has been used in a number of studies to discern the effect of iontophoresis on SC lipid and protein structures, both in vivo and in vitro. In separate studies, human SC was examined in vivo following the delivery of current at 0.1-0.2 mA/cm for 30... 

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