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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
56
13-POS
Board 7
Antichaotropic Salts Can Provoke the Aggregation of PEGylated Liposomes
Tamás Bozó
1
, Tamás Mészáros
2
, Judith Mihály
4
, Attila Bóta
4
, Miklós Kellermayer
1,3
, János
Szebeni
2
, Benedek Kálmán
2
.
1
Semmelweis University, Budapest, Hungary,
2
Semmelweis University, Budapest, Hungary,
3
Hungarian Academy of Sciences - Semmelweis University, Budapest, Hungary,
4
Hungarian
Academy of Sciences, Research Center for Natural Sciences, Budapest, Hungary.
Polyethylene glycol (PEG) and ammonium sulfate (AS) are ingredients widely used to produce
remote loaded, sterically stabilized liposomes (SSL-s). We found that at concentrations about
three times higher than that is used for remote loading, AS can provoke the precipitation of
PEGylated vesicles. The aim of this study was to elucidate this phenomenon by studying the
effect of AS and other salts on PEGylated vesicles.
Precipitation of liposomes was examined by dynamic light scattering and turbidimetry. Phase
contrast and atomic force microscopy imaging were used to assess the morphology of
supravesicular structures. Zeta potential and FTIR experiments were used to assess the surface
charge of the liposomes and conformation of PEG molecules, respectively.
Aggregation of the liposomes was found AS concentration dependent and reversible up to about
1.5 M AS, however at even higher concentrations vesicle fusion occurred. Other antichaotropic
salts (eg. sodium sulfate, magnesium sulfate) also evoked aggregation in a concentration-
dependent manner, while the chaotropic guanidinium-HCl did not precipitate the vesicles.
Aggregation is not surface charge driven as change of zeta potential of liposomes upon AS
addition showed no correlation with it. Threshold concentration of aggregation shifted to lower
values increasing PEG coverage of the liposomes, while PEG-free liposomes did not precipitate
upon addition of AS. FTIR experiments showed that AS reduced the ratio of
trans
and
gauche
configurations of the C-O-C bonds of the of the PEG molecules.
In conclusion, antichaotropic salts may reduce the hydration of PEG polymer chains leading to
aggregation and (at higher concentrations) fusion of sterically stabilized vesicles. Controlled
aggregation of PEGylated liposomes may have both technological and therapeutical
consequences.