Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia

Abstract

Liposomes are potent nanocarriers to deliver chemotherapeutic drugs to tumors. However, the inefficient drug release hinders their application. Thermosensitive liposomes (TSL) can release drugs upon heat. This study aims to identify the optimum 1,2-distearoyl- sn-glycero-3-phosphoethanolamine- N-PEG 2000 (DSPE-PEG 2000) concentration in stealth TSL to improve content release efficiency under mild hyperthermia (HT). TSL were prepared with DSPE-PEG 2000 from 1 to 10 mol%, around 80 nm in size. Quenched carboxyfluorescein (CF) in aqueous phase represented encapsulated drugs. In vitro temperature/time-dependent CF release and TSL stability in serum were quantified by fluorometry. In vivo CF release in dorsal skin flap window chamber models implanted with human BLM melanoma was captured by confocal microscopy. In vitro heat triggered CF release increased with increasing DSPE-PEG 2000 density. However, 6 mol% and higher DSPE-PEG 2000 caused CF leakage at physiological temperature. TSL with 5 mol% DSPE-PEG 2000 were stable at 37 °C, while released 60% CF in 1 min and almost 100% CF in 1 h at 42 °C. In vivo optical intravital imaging showed immediate massive CF release above 41 °C. In conclusion, incorporation of 5 mol% DSPE-PEG 2000 optimized stealth TSL content release triggered by HT.