Sterically stabilised liposomes and related lipid aggregates Fundamental studies on aggragate structure and stability

Detta är en avhandling från Uppsala : Acta Universitatis Upsaliensis

Sammanfattning: Various aspects of and approaches towards the steric stabilisation of liposomes have been investigated, mainly by use of fluorescence techniques and cryo-transmission electron microscopy (cryo-TEM). It is shown that PEG(2000)-lipids can be incorporated in the liposome membrane up to a critical concentration of 8-10 mol% without any observable structural perturbations. Above 10 mol%, a breakdown of the liposome structure into flat lamellar discs was observed. The sterically stabilised liposomes displayed similar, or even reduced, membrane permeability as compared with conventional liposomes. The presence of PEG-lipids in the EPC membrane was shown to affect the liposome-to-micelle transition in mixtures containing OG. Little or no effects of the PEG-lipids were found on the transition in mixtures containing C12E8.The interactions between a number of PEO-PPO-PEO triblock copolymers and PC or PC/Chol liposomes have been investigated. It is shown that these polymers adsorb rapidly onto the liposome surface and induce a substantial increase in membrane permeability as well as structural perturbations. No evidence of an effective steric stabilisation due to the presence of the polymers at the membrane surface was found. This was shown, by the use of a QCM-technique, to be a consequence of the weak interaction between the polymers and the lipid membrane. Dispersions of reversed lipid phases in mixtures of DOPE and PEG-lipids were characterised using cryo-TEM. Dispersions displaying reasonable colloidal stability were obtained and particles exhibiting a periodic dense inner structure were observed.PEG-lipid micelles were characterised mainly using light scattering techniques. Micelle aggregation numbers and hydrodynamic radii were determined as a function of temperature. It is shown that the inter-micellar interactions are dominated by the steric repulsion.PEG-lipid stabilised liposomes loaded with boronated drugs intended for BNCT have been characterised. The drugs were efficiently encapsulated into the liposomes, resulting in a drug precipitation in the water core of the liposomes.