Purpose: Among brain tumors, glioblastoma multiforme (GBM) is the most common and aggressive tumor (WHO grade IV) with a median survival of only 14 months in adults. Light-activated thermosensitive liposomes are based on the formation of phase boundaries in the lipids bilayer at the phase transition of the lipids by photo-triggering systems. Photoactivation is an attractive option for triggering liposomal contents release since it provides a very broad range of adjustable parameters that can be optimized to suit a given application. In particular, spatial and temporal control of the light source provides an additional element of control that can be used to regulate drug release rates. Therefore, we prepared thermosensitive bilamellar liposomes capable of light-activated sequential drug release for the treatment of glioblastoma multiforme and demonstrated its sequential drug release and in vitro and in vivo anticancer ability.
Methods: Light-activated thermosensitive bilamellar liposomes (LATBL) were prepared by sequential lipid film hydration and temperature-controlled membrane extrusion method. Inner cationic liposomes and outer anionic liposomes, contained DPPC and DSPC at a molar ratio of 6:4 and 10:0 respectively, loaded photosensitizer and chemotherapeutics of 1% of total lipid amount (w/w). Size and zeta potential of the LATBL were measured by dynamic light scattering (DLS) instrument and morphology of the LATBL was observed by transmission electron microscope (TEM). The light-activated sequential drug release was studied by different time of laser irradiation.
Results: Inner cationic liposomes (IL) interacted with outer anionic liposomes (OL) by electric charge interaction. The inner liposomes showed positive surface charge, whereas the LATBL showed slightly negative charge, resulting in construction of bilamellar structure through enveloping the IL by the OL. The LATBL showed size of 50 – 200 nm and spherical liposomes morphology, including unilamellar and bilamellar liposomes, in the TEM images. The burst release of drug was observed in twice by different time of laser irradiation, leading to the light-activated sequential drug release.
Conclusion: The light-activated thermosensitive bilamellar liposomal composition was carefully optimized and showed bilamellar liposome structure and sequential light-triggered drug release by laser irradiation. The LATBL is an interesting option for spatial and temporal control of drug release, and in vitro and in vivo studies for GBM therapy will be indispensable to further evaluate the properties of this technology.