Liposomes modifying permeability

Research by P. Scrimin and U. Toneiiato et ai. showed that Zn " was an aiiosteric reguiator of liposomal membrane permeability induced by synthetic template-assembled tripodal polypeptides. Several copies of peptide sequences from the peptaibol family were connected to fr/s(2-aminoethyl)amine (TREN), which is a tripodal metal ion ligand. The resulting tripodal polypeptides were capable of modifying the permeability of liposomal membranes, and their activity was tunable upon metal ion coordination of the TREN subunit. The synthesis of the TREN-based template began with the Stephen reduction of 4-cyanomethylbenzoate followed by the reductive amination of the resulting aldehyde with TREN. 

Tumor cells have an increased vascular permeability and a decrease in their lymphatic drainage system, which leads to the passive accumulation of macromo-lecular drugs in these neoplastie cells. The macromolecules may also contain groups that are preferentially taken up by cancer cells. For example, the presence of folate ions on the surface of boron eontaining hposomes greatly enhances the boron uptake in human KB squamous epithelial cancer cells, which have overexpressed foliate acceptors. " Other examples are the reconstituted LDLs, whieh stiU retain their ability to bond to LDL speeifie sites on the tumor cells. These liposomes and modified LDLs have the ability to deliver massive amounts of to cancer eells and have been... 

Research on oral liposomal delivery systems has moved forward with the development of polymer-modified liposomes. For example, targeted PEGylated liposomes furnished with folic acid for oral delivery were promising, showing enhanced permeability of dextran (used as a marker) across Caco-2 cell monolayers (Anderson et al., 1999). PEG and chitosan-coated lipid nanoparticles were constmcted as oral delivery systems for salmon calcitonin (sCT). The PEG-coated nanoparticles did not alter the transepithelial electrical resistance of Caco-2 cell monolayers, while the chitosan-coated nanoparticles showed a dose-dependent increase in the permeability of dextran across the monolayers (Garcia-Fuentes et al., 2005). It demonstrated that the favourable interaction of the chitosan-coated nanoparticles with intestinal mucosa, together with their permeation enhancing characteristics, could improve the oral absorption of sCT. 

That the fatty acid composition of membranes influences their properties has been demonstrated in several laboratories. In liposomes, which are prepared by gentle but extensive sonication of phospholipid mixtures, permeability to electrolytes and nonelectrolytes is modified by varying the fatty acids of the phospholipids from which the liposomes are made (DeGier et al., 1970 Chen et al., 1971 Scarpa and DeGier, 1971 Demel et al., 1972a,c DeKruyff et al., 1972 Hsia and... 

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