Zonula occludens toxin enhancers

Motlekar NA, Fasano A, Wachtel MS, Youan BB. Zonula occludens toxin synthetic derivative AT1002 enhances in vitro and in vivo intestinal absorption of low molecular weight heparin. J Drug Target 2006 14 321-9. 

Cox, D. S., Raje, S., Gao, H., et al. Enhanced permeability of molecular weight markers and poorly bioavailable compounds across Caco-2 cell monolayers using the absorption enhancer, zonula occludens toxin. Pharm. Res. 19 1680—1688, 2002. 

Low molecular mass permeation enhancers include numerous classes of compounds with diverse chemical properties including detergents, surfactants, N-acetylated x-amino acids, N-acetylated non-a-amino acids, fatty acids, medium-chain mono- and diglycerides, acyl carnitine, alkanoyl cholines, Ca2 + chelating agents, zonula occludens toxins and NO donors. 

Sakai M, Imai T, Ohtake H, Otagiri M (1998) Cytotoxicity of absorption enhancers in Caco-2 cell monolayers. J Pharm Pharmacol 50 1101-1108 Salama NN, Fasano A, Lu R, et al. (2003) Effect of the biologically active fragment of Zonula Occludens toxin, AG, on the intestinal paracellular transport and oral absorption of mannitol. Int J. Pharm 251 113-121... 

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. ... 

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