AbstractNuclear magnetic resonance spectroscopy in conjunction with lanthanide probe ions was used to investigate the interaction of phospholipid vesicles with membrane active compounds such as ionophores, anaesthetics, surfactants and metal ions.
In chapter 1 an introduction to the NMR technique and current progress in the field of model and biological membranes was given. In chapter 2 it was shown that pulsed NMR techniqes gave insight to the effects of calcium, magnesium and lanthanide ions on the motional and physical properties of phospholipid molecules in vesicles.
Membrane permeability induced by both carrier and hannel type ionophores was studied in chapter 3. The kinetics of Pr3+ transport induced by alamethicin 30, A23187, bile salts and phospholipase A was investigated by following time dependent changes in the 1H-NMR spectrum of phospholipid vesicles. The mechanisms involved in the permeability induced by the bile salts and phospholipase was shown to be critical when considering liposomes as carriers of therapeutic drugs delivered by the oral route.
The observation that ethanol and diethyl ether increased the degree of fusion and permeability induced by channels, while chloroform inhibited them suggested a common locus of action on the properties and structure of channel-associated water. These results were discussed in terms of the current theories of general anaesthesia. The influence of cholesterol on the transport properties of alamethicin in the absence and presence of ethanol and chloroform also emphasized the importance of hydrogen-bonds.
The preparation of large unilamellar vesicles by detergent removal gave rise to leaky vesicles. This was attributed to the incomplete removal of detergent by the dialysis method. More efficient methods for their preparation were discussed.
|Date of Award||1984|