1. Liposomes are spherical vesicles composed of a membrane surrounding an aqueous core. Liposomes are used for drug delivery (in the form of genes, peptides, vaccines, siRNA) due to their unique properties. As delivery agents, they are superior to free drugs in regards to antitumor activity, toxicity, therapeutic efficacy, drug resistance, and drug side effects. However, conventional liposomes have several handicaps; they can be rapidly removed from the circulation by body cells, by body enzymes, by stomach acid and by other components of the reticuloendothelial system (RES), which functions to recognize and destroy foreign substances. Stealth liposomes were engineered to help avoid detection by the RES. It was shown that by coating liposomes with polyethylene glycol (PEG), both stability and circulation half-life could be increased. Tetraether Archaeal Liposomes Parkson Lee-Gau Chong, Temple University School of Medicine, DMR 0706410 Drug in aqueous core Conventional Liposome A novel way to increase stability is to use liposomes composed of tetraether macrocyclic lipids isolated from the thermoacidophilic archaeon Sulfolobus acidocaldarius. These are called: Archaeosomes. PLFE lipids form stable archaeosomes: lipids span entire lamellar structure membrane is one molecule thick show high thermal stability show unusually low proton permeability have tight, rigid lipid packing Archaeosomes are better: ♦ temperature and pH stable ♦ resistant to mechanical stress, body enzymes, bile salts, serum proteins. PLFE lipids form stable archaeosomes: lipids span entire lamellar structure membrane is one molecule thick show high thermal stability show unusually low proton permeability have tight, rigid lipid packing Archaeosomes are better: ♦ temperature and pH stable ♦ resistant to mechanical stress, body enzymes, bile salts, serum proteins. S. acidocaldarius thrives at: 65- 85 o C and a pH of 2-3 A constituent of S. acidocaldarius plasma membrane is polar lipid fraction E (PLFE). PLFE contains a mixture of bipolar tetraether lipids (illustrated below). These lipids have a pair of 40-carbon biphytanyl chains; each chain contains up to four cyclopentane rings. The number of cyclopentane rings in each chain increases as growth temperature increases. Typical phospholipid found in conventional liposomes

2. We studied the effect of temperature on the isothermal (k T o ) and adiabatic (k s 0 ) compressibilities of archaeosmes made of PLFE lipids isolated from S. acidocaldarius (growth temperature 65 o C). Compressibilities of PLFE are low, comparable to that for the gel state of dipalmitoylphosphatidylcholine liposomes. Compressibilities increase with increasing temperature, showing a phase transition at ~40 o C. Compressibility of Archaeal Tetraether Liposomes Parkson Lee-Gau Chong 1, Michael Sulc 2, & Roland Winter 2 ( 1 Temple University & 2 Univ. Of Dortmund) Partial specific adiabatic compressibilityPartial specific isothermal compressibility Density (ρ), ultrasound velocity (u), thermal expansion coefficient (  ) and heat capacity (Cp) were measured. o is the partial specific volume.  is the compressibility coefficient.