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

1
Tetraether Archaeal Liposomes Parkson Lee-Gau
Chong, Temple University School of Medicine, DMR
0706410
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.
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
S. acidocaldarius thrives at 65-85oC and a pH of
2-3

• 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 stable
• pH stable
• resistant to mechanical stress, body
• enzymes, bile salts, serum proteins.

A constituent of the S. acidocaldarius plasma
membrane is polar lipid fraction E (PLFE). PLFE
contains a mixture of bipolar tetraether lipids.
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.
2
Tetraether Archaeal Liposomes Parkson Lee-Gau
Chong, Temple University School of Medicine, DMR
0706410
Autoclaving is a very effective decontamination
method. The ability to maintain vesicle
integrity after autoclaving would be a desirable
feature for systemic use of liposomes.
We found that PLFE-based archaeosomes are
remarkably stable against multiple autoclaving at
pH 4-10 when compared to conventional liposomes.
Stability was measured in terms of particle size,
size distribution and vesicle morphology using
dynamic light scattering and transmission
electron microscopy This result adds one more
reason for exploring bipolar tetraether
archaeosomes as stable effective drug delivery
vehicles. (Z0 size before autoclaving, Z1, Z2,
Z3 size after first, second and third
autoclaving all particle sizes in nm)
Conventional lipids used pH Z0 Z1 Z2 Z3
DMPC 4.0 180.0 389.1 307.2 476.2
7.2 167.3 234.6 322.5 399.7
10.0 171.7 196.9 258.7 322.5
POPC 4.0 180.5 210.3 241.6 901.0
7.2 174.5 224.7 196.9 676.3
10.0 225.7 840.5 gt2000 gt2000
Archael lipids growth temp pH Z0 Z1 Z2 Z3
PLFE (65C) 4.0 156.7 166.3 165.7 163.7
7.2 159.4 156.4 157.2 159.3
10.0 152.8 146.4 148.7 158.9
PLFE (78C) 4.0 216.8 222.8 207.1 200.7
7.2 210.2 234.1 202.4 208.3
10.0 213.4 202.5 230.3 222.6
mm
Conventional stealth liposomes before autoclaving
average particle size 200 nm
PLFE-based stealth archaeosomes before autoclaving
Conventional stealth liposomes after 1
autoclaving average particle size 1700 nm
PLFE archaeosomes before autoclaving
PLFE-based stealth archaeosomes after 6 cycles of
autoclaving
PLFE archaeosomes after 6 cycles of autoclaving
Micrograph of S acidocaldarius
http//www.tms.org/pubs/journals/JOM/0607/Fig1b.gi
f liposome http//www.lyposphere.com/liptra2.JPG
Archaea tree http//paleobio.org/agc/MEH/MEHfig
2.gif