Oral epithelium lipophilic drugs

The skin is biologically intended to be a barrier. Evading this barrier is not easy, because drugs must traverse dead epithelium and live dermis the former is hydrophobic, while lipophilic drugs tends to form a reservoir in the latter. As in oral transmucosal administration, potent drugs, with modest requirements for mass absorbed and reasonable lipophilicity, are the best candidates for transdermal delivery. Fentanyl, nicotine, and scopolamine are good examples. 

Penetration enhancers are low molecular weight compounds that can increase the absorption of poorly absorbed hydrophilic drugs such as peptides and proteins from the nasal, buccal, oral, rectal, and vaginal routes of administration [186], Chelators, bile salts, surfactants, and fatty acids are some examples of penetration enhancers that have been widely tested [186], The precise mechanisms by which these enhancers increase drug penetration are largely unknown. Bile salts, for instance, have been shown to increase the transport of lipophilic cholesterol [187] as well as the pore size of the epithelium [188], indicating enhancement in both transcellular and paracellular transport. Bile salts are known to break down mucus [189], form micelles [190], extract membrane proteins [191], and chelate ions [192], While breakdown of mucus, formation of micelles, and lipid extraction may have contributed predominantly to the bile salt-induced enhancement of transcellular transport, chelation of ions possibly accounts for their effect on the paracellular pathway. In addition to their lack of specificity in enhancing mem-... 

Drug distribution in such sites or compartments is a complex process that depends on the systemic circulation concentration and subsequent passage across single cell endothelial or epithelial membranes with specialized physical and molecular barrier functionality. For certain orally administered AIDS medications (e.g., zidovudine and didanosine), oral absorption is limited because of poor absorption from the G1 tract, enzymatic biotransformation in the intestinal epithelium, or first-pass effects (Sinko et al., 1995, 1997). For other AIDS drugs (e.g., protease inhibitors), oral absorption may be complete however, drug distribution into the brain is limited by drug efflux proteins, which promiscuously interact and translocate lipophilic substrates back into blood as they diffuse into the BBB endothelium (Edwards et al., 2005 Kim et al., 1998). 

The requirement that the chelating agent and its iron(III) chelate not Interfere with cellular biochemistry must be considered. Drugs which can pass through the gastrointestinal epithelium are also likely to penetrate other cell membranes. A drug which is suitable for oral administration may therefore have undesir-abel side effects unless its lipophilic character is rapidly... 

---