Thermosensitive liposomes encapsulating hypericin: Characterization and photodynamic efficiency

The potent photodynamic properties of Hypericin (Hyp) elicit a range of light-dose-dependent anti-tumor activities. However, its low water solubility hampers its broad application. Therefore, the administration of Hyp into biological systems requires drug carriers that would enable sufficient bioavailability. Stimuli-triggered nanocarriers, which are sensitive to endogenous or exogenous stimuli, have become an attractive replacement for conventional therapeutic regimens. Herein, we produced optimized Hyp thermosensitive liposomes (HypTSL), self-assembled from DPPC, DSPC, DSPE-PEG2000. Hyp-TSL displayed a hydrodynamic diameter below 100 nm with an adequate encapsulation efficiency of 94.5 % and good colloidal stability. Hyp-TSL exhibited thermal sensitivity over a narrow range with a phase transition temperature of 41.1 degrees C, in which liposomal destruction was evident in AFM images after elevated temperature above the phase transition temperature. The uptake of TSL-Hyp into MDA-MB-231 cells was significantly increased with hyperthermic treatment of 42 degrees C when compared to the uptake at a average physiological temperature of 37 degrees C. Consequent enhancement of cellular reactive oxygen species was observed after hyperthermic treatment at 42 degrees C. The half-maximal inhibitory concentration of Hyp TSL was reduced by 3.8 fold after hyperthermic treatment at 42 degrees C in comparison to treatment at 37 degrees C. Hyp-TSL were considered safe for intravenous applications as compared by hemocompatibility studies, where coagulation time was <50 s and hemolytic potential was <10%. Conclusively, the enhancement in tumor drug availability correlated with improved therapeutic outcomes.

Automated summary

Optimized Hyp thermosensitive liposomes (HypTSL) demonstrated good colloidal stability and high encapsulation efficiency, exhibiting thermal sensitivity at 42 degrees Celsius. The uptake of Hyp-TSL by MDA-MB-231 cells and cellular reactive oxygen species production were significantly enhanced at 42 degrees Celsius, leading to improved tumor drug availability and therapeutic outcomes.