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TAT peptide was attached to the surface of plain and PEGylated liposomes. These TAT peptide-modified liposomes have been shown to translocate into a variety of normal and cancer cells if a non-hindered interaction between the cell surface and liposome-attached TAT peptide was made possible. TAT peptide-liposomes translocated into cells remain intact within first few hours as proved by a co-localization of fluorescent markers entrapped inside liposomes and incorporated into the liposomal membrane. After 2 hours liposomes had slowly migrating towards cell nuclei. Liposomes had completely disintegrated with their inner marker released by approximately 9 hours. TAT peptide-liposomes were made slightly cationic by adding up to 10 mol %. of a cationic lipid (DOTAP). These slightly cationic liposomes were non-toxic towards cells, formed firm complexes with DNA (plasmid encoding for the formation of the Green Fluorescent Protein), and efficiently transfected a variety of cells. TAT peptide-liposomes can be considered as promising carriers for the non-endocytotic intracellular delivery of drugs and DNA.

In this study, we have investigated the potential of trans-activating transcriptional activator peptide (TATp)-modified liposomes to enhance the delivery of the model gene, plasmid encoding for the green fluorescent protein (pEGFP-N1), to human brain tumor U-87 MG cells in vitro and in an intracranial model in nude mice. The TATp-lipoplexes were characterized at lipid/DNA (+/-) charge ratios of 0.2, 5, 10, and 20 for size analysis and DNA complexation. The size distribution of DNA-loaded TATp-liposomes was narrow and the DNA complexation was firm at lipid/DNA (+/-) charge ratios of 5 and higher. TATp-lipoplexes had demonstrated an enhanced delivery of pEGFP-N1 to U-87 MG tumor cells in vitro at lipid/DNA (+/-) charge ratios of 5 and 10. In vivo transfection of intracranial brain tumors by intratumoral injections of TATp-lipoplexes showed an enhanced delivery of pEGFP-N1 selectively to tumor cells and subsequent effective transfection compared to plain plasmid-loaded lipoplexes. No transfection (green fluorescence of the GFP) was noted in the normal brain adjacent to tumor.

Hydraphile compounds are shown to be cytotoxic to Gram-negative and Gram-positive bacteria, yeast, and mammalian cells. Their cellular toxicity compares favorably with other synthetic ionophores and rivals that potency of natural antibiotics. The effects of structural variations on toxicity are described. The effects of these variations correlate well with previous studies of ion transport in liposomes. Whole cell patch clamping with mammalian cells confirms a channel mechanism in living cells suggesting that this family may comprise novel and flexible pharmacological agents.