Archaeobacterial Ether Lipid Liposomes (Archaeosomes) as Novel Vaccine and Drug Delivery Systems

Abstract

Liposomes are artificial, spherical, closed vesicles consisting of one or more lipid bilayer(s). Liposomes made from ester phospholipids have been studied extensively over the last 3 decades as artificial membrane models. Considerable interest has been generated for applications of liposomes in medicine, including their use as diagnostic reagents, as carrier vehicles in vaccine formulations, or as delivery systems for drugs, genes, or cancer imaging agents. The objective of this article is to review the properties and potential applications of novel liposomes made from the membrane lipids of Archaeobacteria (Archaea). These lipids are unique and distinct from those encountered in Eukarya and Bacteria. Polar glycerolipids make up the bulk of the membrane lipids, with the remaining neutral lipids being primarily squalenes and other hydrocarbons. The polar lipids consist of regularly branched, and usually fully saturated, phytanyl chains of 20, 25, or 40 carbon length, with the 20 and 40 being most common. The phytanyl chains are attached via ether bonds to the sn-2,3 carbons of the glycerol backbone(s). It has been shown only recently that total polar lipids of archaeobacteria, and purified lipid fractions therefrom, can form liposomes. We refer to liposomes made with any lipid composition that includes ether lipids characteristic of Archaeobacteria as archaeosomes to distinguish them from vesicles made from the conventional lipids obtained from eukaryotic or eubacterial sources or their synthetic analogs. In general, archaeosomes demonstrate relatively higher stabilities to oxidative stress, high temperature, alkaline pH, action of phospholipases, bile salts, and serum proteins. Some archaeosome formulations can be sterilized by autoclaving, without problems such as fusion or aggregation of the vesicles. The uptake of archaeosomes by phagocytic cells can be up to 50-fold greater than that of conventional liposome formulations. Studies in mice have indicated that systemic administration of several test antigens entrapped within certain archaeosome compositions give humoral immune responses that are comparable to those obtained with the potent but toxic Freund's adjuvant. Archaeosome compositions can be selected to give a prolonged, sustained immune response, and the generation of a memory response. Tissue distribution studies of archaeosomes administered via various systemic and peroral routes indicate potential for targeting to specific organs. All in vitro and in vivo studies performed to date indicate that archaeosomes are safe and do not invoke any noticeable toxicity in mice. The stability, tissue distribution profiles, and adjuvant activity of archaeosome formulations indicate that they may offer a superior alternative to the use of conventional liposomes, at least for some biotechnology applications.

Functional Reconstitution of the Integral Membrane Enzyme, Isoprenylcysteine Carboxyl Methyltransferase, in Synthetic Bolalipid Membrane Vesicles

“…Studies of biogenic and synthetic variants of these unusual membrane materials demonstrate that bolalipid membranes are less permeable and more durable than membranes composed of monopolar lipids (8)(9)(10)(11)(12)(13). This unique combination of properties has ignited interest in their use as non-polymeric membrane stabilizing agents in applications such as drug delivery and membrane protein-based biosensors (5,12,14,15).…”

Characterization of Inverted Membrane Vesicles from the Halophilic Archaeon Haloferax volcanii

“…Studies involving archaeosomes, i.e., liposomes prepared from archaeal phospholipids, have shown that membranes containing these chemically unique structures are more rigid, proton and sodium ion impermeant, lipase resistant and better able to withstand extremes of pH, temperature and salinity than membranes prepared from bacterial or eukaryal phospholipids [cf. 34,41].…”

Recent advances in the development of novel mucosal adjuvants and antigen delivery systems

“…14,15,21,29,37,[54][55][56] Also, the unique characteristics of archaeal polar lipids (ether bonds, saturated phytanyl chains, membrane spanning vesicle layer) confer better stability (no oxidation, resistance to phospholipases and bile salts, stability over a wide range of pH and in serum, and better thermal stability) to the archaeosomes/AMVAD system, compared with ester lipid liposomes and cochleates. 35,36,44,45,57,58 Further, AMVAD formulations are stable at 5°C for at least one year. In addition, the protocols developed for preparing liposomes are generally applicable for making archaeosome formulations.…”

“…Archaeal polar lipids comprise of regularly branched, 5-carbon repeating units making up the usually fully saturated (with few exceptions) isopranoid chains which are attached via ether bonds to the sn-2,3 carbons of the glycerol backbone. [42][43][44] Closed vesicles (i.e., liposomes) made from archaeal polar lipid extracts are referred to as archaeosomes [44][45][46] to distinguish them from liposomes made from ester phospholipids.…”