O

O

O

OH

OH

OH

O R3

CH3CH3 CH

3CH3

CH3CH3

O

O

CH3

CH3

CH3 CH3 CH3 CH3

CH3

PO4

R1

CH3

OH

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 .

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.

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

ConventionalLiposome

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.

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-

85oC and a pH of 2-3S. acidocaldarius thrives at: 65-85oC 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.

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

We studied the effect of temperature on the isothermal (kTo) and adiabatic (ks

0) compressibilities of archaeosmes made of PLFE lipids isolated from S. acidocaldarius (growth temperature 65oC). 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 ~40oC.

We studied the effect of temperature on the isothermal (kTo) and adiabatic (ks

0) compressibilities of archaeosmes made of PLFE lipids isolated from S. acidocaldarius (growth temperature 65oC). 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 ~40oC.

Compressibility of Archaeal Tetraether LiposomesParkson Lee-Gau Chong1, Michael Sulc2, & Roland Winter2

(1Temple University & 2Univ. Of Dortmund)

20 30 40 50 60 70 80 90

2,9x10-10

3,0x10-10

3,1x10-10

3,2x10-10

3,3x10-10

3,4x10-10

3,5x10-10

3,6x10-10

o

S /

mL

g-1 P

a-1

Temperature T / °C20 30 40 50 60 70 80 90

2,9x10-10

3,0x10-10

3,1x10-10

3,2x10-10

3,3x10-10

3,4x10-10

3,5x10-10

3,6x10-10

o

S /

mL

g-1 P

a-1

Temperature T / °C

Partial specific adiabatic compressibility Partial specific isothermal compressibility

20 30 40 50 60 70 80 90

3,0x10-10

3,2x10-10

3,4x10-10

3,6x10-10

3,8x10-10

4,0x10-10

o

T /

mL

g-1 P

a-1

Temperature T / °C20 30 40 50 60 70 80 90

3,0x10-10

3,2x10-10

3,4x10-10

3,6x10-10

3,8x10-10

4,0x10-10

o

T /

mL

g-1 P

a-1Temperature T / °C

0

o0

oo 1

2ρ

uvβp

v=

n= S,

S

SS

lipidooSS βv=

00

o

0

oo

00

20oo 2

p,

p

p,ST cρ

cv

cρ

Tα+=

lipidooTT βv=

00

o

0

oo

00

20oo 2

p,

p

p,ST cρ

cv

cρ

Tα+=

Density (ρ), ultrasound velocity (u), thermal expansion coefficient () and heat capacity (Cp) were measured. o is the partial specific volume. is the compressibility coefficient.