Photothermal Liposomal Drug Delivery Systems - Physicochemical Aspects in Particle Characterization and Drug Release from Light-Sensitive Drug Carriers

Liposome is a phospholipid structure that surrounds its aqueous cavity with a lipid bilayer. Hydrophilic drug molecules can be encapsulated in liposomes and delivered to a given target. Ideally, liposomes are internalized by the target cell via endocytosis and the hydrophilic drug is released therein. In many cases, liposomes reach their target cell but the rate of passive release remains insufficient. Luckily, this challenge can be tackled with a suitable triggering mechanism. One option is to use light. Light triggered drug release can be obtained with several strategies. One of the most interesting methods is to employ materials that convert light into heat. In this case, a photothermal agent absorbs light and releases the absorbed energy as heat. Such materials include a wide selection of gold nanoparticles that can be tuned to any relevant wavelengths by adjusting their size and shape. Another example is the fluorescent dye indocyanine green (ICG). It absorbs in the near infrared region that is safe for tissue irradiation (i.e. at the physiological window). A photothermal liposomal drug delivery system is composed of drug-encapsulated liposomes with photothermal agents. In essence, a lipid bilayer prevents drug from releasing below its phase transition temperature. However, when the photothermal agents heat up locally, the drug molecules are released as the bilayer undergoes a phase transition. This thesis addresses photothermal liposomal drug delivery systems from the physicochemical point of view and provides some new methods to characterize such systems. This work can be divided in three sections. In the first section, liposomes were coupled with photothermal agents and light-inflicted changes in the lipid bilayer were monitored with the quartz crystal microbalance and fluorescence spectroscopy. The main effect was the thermal phase transition in the lipid bilayer followed by the contents release. In the second section, methods of liposome detection were examined. Surface plasmon resonance imaging microscopy (SPRIM) was used to determine the number of encapsulated gold nanoparticles residing inside the liposomes with a new analysis method. In the third section, the prospects of surface engineering of liposomes was investigated with the addition of lipid-bound poly(ethylene glycol) (PEG). A new method, based on laurdanC, was developed to monitor the shape of the particulates. In addition, PEGylation caused changes in the phase transition behavior and shape of the lipid particulates. These features can provide new opportunities for drug delivery. These could be e.g. drug release systems with multiple release sequences and shape-shifting drug carriers with trigger polymers.