| dc.description.abstract | The Interactions between Phosphatidylcholine Vesicles and Ionic Surfactants:
Effects of Temperature and PEG-Lipid
Student: Shis-Chi Chu Advisor: Heng-Kwong Tsao
Department of Chemical and Materials Engineering
National Central University
ABSTRACT
Liposomes are widely used as drug carriers due to their special structure and properties. Nevertheless, the in vivo stability of liposomes poses limitations on their applications. For example, an enough amount of biosurfactant can solubilize liposomes. In general, liposome solubilization can be described by the three-stage hypothesis, including vesicular regime, vesicle-micelle coexistence, and mixed micellar regime. In this thesis, we focus on the first stage and study the partition of ionic surfactant between the bilayer phase and the aqueous phase.
Phosphatidylcholine vesicles are prepared by the extrusion method without addition of buffer and salt. The bilyer/aqueous phase partition coefficient K and the surfactant/lipid molar ratio Re of of six ionic surfactants are then determined by conductivity measurements, which are based on the fact the vesicle acts as a trap of charge carriers. The main purpose of the thesis is to investigate the effects of temperature and PEG-lipid on the partition coefficient. The experimental data can be well represented by the simple thermodynamic model and the thermodynamic parameters satisfy the thermodynamic consistency.
The partition coefficient is found to decline with increasing temperature. This consequence indicates that the mean interaction energy per surfactant molecule in the aqueous phase mw0 is greater than that in the bilayer mb0. The difference of the mean interaction energy is O(kT) and rises as the chain length is increased. Because the change in temperature influences the surfactant incorporation into the bilayer more than the formation of micelles, the solubilizing ability Reb also decreases in accord with the partition coefficient. For a specified hydrophilic head, we observe that the partition coefficient grows with the alkyl chain length. According to our experimental results, the increment of the mean interaction energy per alkyl group is O(kT), which agrees with the thermodynamic prediction.
It is known that the physical stability of a liposome containing a few PEG-lipid is enhanced due to the steric repulsion. Biologically, a stealth liposome is also obtained because PEG-lipid provides the opportunity of escaping from macrophage uptake. In this study, a liposome containing 1% PEG (2000)-lipid is prepared. In comparison with liposomes without PEG-lipid, the mean radius of such liposomes is smaller. In addition, the thermodynamic parameters K and Reb are increased. This result indicates that PEG-lipid lowers the mean interaction energy in the bilayer phase and therefore leads to a higher partition coefficient. However, the ability of resisting surfactant solubilization is also enhanced. Therefore, we conclude that addition of PEG-lipid provides another stability mechanism. | en_US |