Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia.

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Drug Delivery Systems

Background:

• Liposomes are effective nanocarriers for chemotherapy, but inefficient drug release limits their clinical use.
• Thermosensitive liposomes (TSL) offer controlled drug release upon heating, a strategy known as mild hyperthermia (HT).
• Optimizing the composition of stealth TSL is crucial for improving drug release efficiency under HT.

Purpose of the Study:

• To determine the optimal concentration of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG(2000) (DSPE-PEG(2000)) in stealth TSL for enhanced content release under mild hyperthermia (HT).

Main Methods:

• TSL formulations with varying DSPE-PEG(2000) concentrations (1-10 mol%) were prepared and characterized for size (~80 nm).
• In vitro studies quantified temperature/time-dependent carboxyfluorescein (CF) release and serum stability using fluorometry.
• In vivo studies utilized confocal microscopy in dorsal skin flap window chamber models with human BLM melanoma to assess CF release.

Main Results:

• In vitro heat-triggered CF release increased with higher DSPE-PEG(2000) concentrations.
• DSPE-PEG(2000) concentrations of 6 mol% and above led to premature CF leakage at physiological temperatures (37°C).
• TSL with 5 mol% DSPE-PEG(2000) demonstrated stability at 37°C and released 60% CF within 1 minute and nearly 100% within 1 hour at 42°C. In vivo imaging confirmed rapid CF release above 41°C.

Conclusions:

• Incorporating 5 mol% DSPE-PEG(2000) optimizes stealth TSL for triggered content release by mild hyperthermia (HT).
• This optimized formulation achieves stability at physiological temperatures while enabling rapid and efficient drug release upon mild hyperthermia.
• The findings suggest a promising strategy for enhancing the efficacy of liposomal chemotherapy through controlled thermal triggers.