Abstract
Thermoresponsive or thermosensitive liposomes (TSLs) have been developed to allow for a sudden release of a previously entrapped drug within cancer tissue subjected to mild hyperthermia. To this end, TSLs must be quite stable and impermeable up to 39°C but become substantially leaky at about 42°C. The most advanced, LTSL, formulation, consists of DPPC, 10 mol% lyso-SPC, and 4 mol% PEG-DSPE. Over decades, its mode of action has been explained by detergent-like pores formed by the lysolipid in the appearing fluid phase and a quasi-ideal mixing in the gel state. What we refer to as the lysolipid paradox is that the exactly opposite temperature triggering had been described for other detergent-like molecules before: Already at concentrations where they do not form any pores in the fluid phase, they would trigger liposome disintegration upon cooling to form the gel phase. We have recorded a phase diagram of DPPC-lyso-SPC revealing that the lysolipid content of LTSLs, 10 mol%, is very close to an eutectic composition. This finding has far-reaching consequences for TSL action and its detailed thermodynamic understanding and resolves the “lysolipid paradox”. Lyso-SPC does not mix ideally with DPPC in the gel phase bilayer, it largely ideally DE-MIXES from the bilayer to form a stoichiometric 1:1 mol complex with DPPC. It had been found for a related system before that an interdigitated gel phase is formed at 1:1 lysolipid and DPPC but this interdigitated gel phase has, to our knowledge, not been recognized to be present in the LTSL and crucial for its mode of action.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
