Membrane polycationic penetration

The numerous negative charges are significant in several respects (1) they contribute to the poor membrane penetrability—heparin is ineffective when applied by the oral route or topically onto the skin and must be injected (2) attraction to positively charged lysine residues is involved in complex formation with ATIII (3) they permit binding of heparin to its antidote, protamine (polycationic protein from salmon sperm). [Pg.144]

Some drug absorption enhancers are capable of loosening tight junctions (zonula occludens) and thereby facilitate paracellular absorption of drug molecules and improve the bioavailability of active pharmaceutical ingredients with low membrane permeability. The penetration enhancers include chelating agents [e.g., ethylenediaminetetraacetic acid), toxins [e.g., zonula occludens toxin), plant-derived materials [e.g., aloe vera gel), and cationic polymers. Polycationic lipophilic-core dendrons, which form lipophilic ion-pairs with heparin, were studied as a system for oral delivery of heparin. ... [Pg.308]