Small-Angle Neutron Scattering Study of Temperature-Induced Structural Changes in Liposomes

Abstract

Liposomes of specific artificial phospholipids, such as Pad-PC-Pad and Rad-PC-Rad, are mechanically responsive. They can release encapsulated therapeutics via physical stimuli, as naturally present in blood flow of constricted vessel segments. The question is how these synthetic liposomes change their structure in the medically relevant temperature range from 22 to 42 °C. In the present study, small-angle neutron scattering (SANS) was employed to evaluate the temperatureinduced structural changes of selected artificial liposomes. For Rad-PC-Rad, Pad-Pad-PC, Sur-PC-Sur, and Sad-PC-Sad liposomes, the SANS data have remained constant because the phase transition temperatures are above 42 °C. For Pad-PC-Pad and Pes-PC-Pes liposomes, whose phase transitions are below 42 °C, the q-plots have revealed temperature-dependent structural changes. The average diameter of Pad-PC-Pad liposomes remained almost constant, whereas the eccentricity decreased by an order of magnitude. Related measurements using transmission electron microscopy at cryogenic temperatures, as well as dynamic light scattering before and after the heating cycles, underpin the fact that the non-spherical liposomes flatten out. The SANS data further indicated that, as a consequence of the thermal loop, the mean bilayer thickness increased by 20%, associated with the loss of lipid membrane interdigitation. Therefore, Pad-PC-Pad liposomes are unsuitable for local drug delivery in the atherosclerotic human blood vessel system. In contrast, Rad-PC-Rad liposomes are thermally stable for applications within the human body.

Effects of lipid bilayer encapsulation and lipid composition on the catalytic activity and colloidal stability of hydrophobic palladium nanoparticles in water

“…The melting transition from the liquid crystalline phase to amorphous phase takes place at 54.5 ± 1.5 °C ( T m ). 46–49…”

“…The melting transition from the liquid crystalline phase to amorphous phase takes place at 54.5 AE 1.5 C (T m ). [46][47][48][49] The catalytic activity and selectivity of the DSPC-PdNP LNAs were examined at different temperatures in water. By using 1octene as substrate, the catalytic activity of the LNAs was analyzed at 1, 3, 6, and/or 24 hours at 0, 22, 37, and 55 C, which are water freezing point, room temperature (close to gel-toliquid crystalline transition temperature (T g-to-l ) of DSPC), biological temperature, and melting transition temperature (T m ) of DSPC, 46,49 to see the potential effect of the phase transition of the DSPC liposome bilayers.…”

“…Lipid bilayers composed of diacyl phosphatidylcholines exhibit temperature dependent chain dynamics. [45][46][47] Although the exact temperatures at which a change in dynamics occurs are different depending on the structure of lipids, there is a general trend most phosphatidylcholines follow. At low temperatures, the acyl chains occupy an ordered gel phase characterized by restricted movement of the acyl chains and a narrowing of the phospholipid bilayer.…”

Small-Angle Neutron Scattering for Studying Lipid Bilayer Membranes

“…Cardiolipin bilayer membranes have been studied [ 139 ] as well as those formed by sphingomyelins [ 140 ], the GM3 ganglioside [ 141 ], and lipopolysaccharides extracted from cells [ 142 , 143 ]. More novel lipids have been studied using SANS, such as fully artificial ones [ 144 ] and siloxane phosphocholines [ 145 ]. SANS also provides the important membrane thickness needed for understanding the dynamics of lipid bilayers that have been measured by NSE [ 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 ], although the information reported about the structure may not be as detailed as what is found in a study dedicated to membrane structure.…”

Intravenous Hemostats: Foundation, Targeting, and Controlled-Release

“…In addition, in vitro toxicity test results 129 showed minimal immunotoxicity of Rad-PC-Rad liposomes. Matviykiv et al 130 used small-angle neutron scattering (SANS) to study the Pad-PC-Pad and Rad-PC-Rad over the medical temperature range (22−42 °C). The results showed that Pad-PC-Pad was not suitable for local arterial administration, and Rad-PC-Rad was more suitable for human application due to its thermal stability.…”