Pharmaceutical Nanotechnology led by Professor Timo Laaksonen on controlled drug release and delivery using modern methods and materials. Particular interest lies in using light to both monitor nanomaterial behavior and to trigger e.g. drug release processes.
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Laser use: Light-triggered drug release studies from light-activated liposomes. ML8500 with 808 nm wavelength was used to induce the release of calcein from liposomes under different temperatures. The effect of different type of lipids on liposomal release properties was investigated.
Link to the study:
Background
The proper delivery and release of therapeutic drugs to a specific site or cell type is one of the main challenges in the treatment of diseases. Liposomes, which are vesicles composed of lipids, serve as carriers for drug delivery thanks to their long circulation time. This results to reduced toxicity in healthy tissues and improved therapeutic efficacy of encapsulated drugs. However, conventional liposomes can often be even too stabile, leading to insufficient drug release at the target site. Light activation can offer a solution for this dilemma to achieve both sufficient stability and efficient drug release.
Laser light is used to release liposomal contents at the target site, offering time- and site-specific control for the drug release. For this purpose, stimuli-responsive molecules, such as clinically approved indocyanine green, are attached to the liposomal surface, generating heat upon to near-infrared light irradiation leading to the rapid release of liposomal contents. In addition, positively charged (cationic) liposomes can offer better drug uptake by tumor cells, since cancer cells typically have slightly higher negative surface charge because of a higher rate of glycolysis.
Study execution
The purpose of the study was to determine optimal lipid composition for light-triggered drug release. Calcein was used as a cargo molecule inside liposomes since its fluorescence could be used to determine the amount of released calcein. The ICG and calcein-loaded cationic liposomes were fabricated via a thin film hydration method. Calcein release from liposomes after light activation was studied using ML8500 automated biomedical illumination instrument. The effect of several different lipids on liposomal leakiness, stability, and light-induced release was investigated.
Results
Unsaturated lipids (DOTAP) in the liposomal structure caused kink formations and resulted in fluid lipid bilayer. These liposomes were very leaky and calcein release happened already at 32 °C without light activation.
In contrast, liposomes with cholesterol in the lipid bilayer made liposomes sturdy and significantly decreased fluidity of liposomes. It also made liposomes unresponsive to light, as liposomes did not release calcein even when temperature reached 50 °C after light activation with the ML8500.
The most optimal thermosensitive liposome composition was achieved with saturated lipids (DPTAP), resulting in ordered lipid bilayer and stable liposomes at body temperature (37 °C). Importantly, liposome contents were successfully released after light activation by the ML8500.
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Related Publications
The effect of light sensitizer localization on the stability of indocyanine green liposomes
Tatu Lajunen, Riikka Nurmi, Danny Wilbie, Teemu Ruoslahti, Niklas G. Johansson, Ossi Korhonen, Tomasz Rog, Marika Ruponen, Arto Urtti
Journal of Controlled Release, 2018, 284
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