Eutectic Resolves Lysolipid Paradox in Thermoresponsive Liposomes.

Area of Science:

• Drug Delivery Systems
• Lipid Bilayer Research
• Materials Science

Background:

• Thermosensitive liposomes (LTSLs) are crucial for temperature-triggered drug delivery.
• Understanding the 'lysolipid paradox' is key to optimizing LTSL function.
• Current models do not fully explain lysolipid behavior in LTSLs.

Purpose of the Study:

• To elucidate the molecular mechanisms of drug release from LTSLs.
• To explain lysolipid's role in drug retention and release.
• To investigate LTSL annealing and incomplete drug release.

Main Methods:

• Differential scanning calorimetry
• Pressure perturbation calorimetry
• Small- and wide-angle X-ray scattering (SAXS/WAXS)

Main Results:

• LTSLs with 10 mol% monostearyl lysophosphatidylcholine (MSPC) exist at a eutectic point near 41°C.
• A gel phase with depleted MSPC and interdigitated MSPC-rich domains coexist below 41°C.
• Melting at 41°C creates transient pores due to high local MSPC, enabling drug release.

Conclusions:

• The 'lysolipid paradox' is explained by MSPC's safe storage in interdigitated domains.
• Drug release is mediated by transient pores formed upon melting of MSPC-rich domains.
• Membrane sealing occurs as MSPC redistributes, limiting total drug release.