Disc formation in cholesterol-free liposomes during phase transition

Abstract

Cryogenic transmission electron microscopy (cryo-TEM) images of lysolipid-containing thermosensitive liposomes (LTSL) revealed that open liposomes and bilayer discs appeared when liposomes were cycled through the gel (Lbeta') to liquid-crystalline (Lalpha) phase transition. The amount of bilayer discs generated was dependent on the combined presence of PEG-lipid and lysolipid in the membrane. We hypothesize that micelle-forming membrane components stabilize the rim of bilayer openings and membrane discs that form when liposomes are cycled through TC.

Review of current trends in enhancing bioavailability of poorly water soluble drugs by liposomal interventions

“…The LTSL formulation was originally composed of DPPC/lyso-PC/DSPE-PEG 2000 90:10:4 (mol/mol) but was modified slightly in recent years [33]. The surfactant, lyso-PC, mediates drug release around T m by formation of lysolipid-stabilized membrane pores [33], [42], [43]. The release rate of doxorubicin from LTSL at 41.3°C was 80% in 20 seconds.…”

“…LTSL was the first TSL formulation suitable for use in the intravascular drug release approach. This formulation is characterized by ultrafast drug release upon heating, although incorporation of surfactants in the formulation decreases vesicle stability around T m [42]. Moreover, approximately 70% of lysolipid was found to dissociate from the formulation within one hour post injection [50].…”

Thermosensitive liposomal drug delivery systems: state of the art review

“…Lipid-grafted PEG (eg, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(PEG)-2000, DSPE-PEG 2000 , Figure 5A) is commonly used in liposomes to create a steric barrier for inhibition of uptake by the reticuloendothelial system and increased blood circulation time, [47][48][49] but also potentially affects vesicle stability ( Figure 5B). 50 In addition to phospholipid composition, the manifestation of heat-triggered drug release depends to some degree on the drug molecule encapsulated ( Figure 4C), 28,51,52 vesicle size, 51 and the presence of serum components. 45,52 In vitro and in vivo behavior of selected formulations Until now distinct liposomal formulations have been described, which will be discussed in detail in this section (Table 1).…”

“…10 The surfactant, lyso-PC ( Figure 5A), mediates drug release around T m by formation of lysolipid-stabilized membrane pores. 10,50,58 The release rate of doxorubicin from LTSL at 41.3°C was 80% in 20 seconds. 14 In comparison, TTSL released only 40% of its doxorubicin content in 30 minutes on heating to 42°C.…”

“…This formulation is characterized by ultrafast drug release upon heating, although incorporation of surfactants in the formulation decreases vesicle stability around T m . 50 Moreover, approximately 70% of lysolipid was found to dissociate from the formulation within one hour post injection. …”