Ultrasound-mediated destabilization and drug release from liposomes comprising dioleoylphosphatidylethanolamine

Abstract

Liposomal encapsulation of doxorubicin (DXR) improves tumor accumulation and reduces adverse effects. One possible strategy for further optimization of this delivery technology would be to design the liposome carrier to release its content within the tumor tissue in response to specific stimuli such as ultrasound (US). In this study, the tumor uptake properties and therapeutic efficacy of 1,2 distearoyl-sn-glycero-3-phosphatidylethanolamine-based liposomes containing DXR were investigated in nude mice bearing tumor xenografts. The liposomal DXR formulation alone showed no inhibitory effect on tumor growth. However, upon exposure to low frequency US in situ inhibition of tumor growth was demonstrated.

Sonosensitive dioleoylphosphatidylethanolamine-containing liposomes with prolonged blood circulation time of doxorubicin

“…We recently demonstrated that incorporation of DOPE into liposome bilayers drastically enhanced sonosensitivity compared to DSPE-based liposomes and standard liposomal DXR, respectively (Evjen et al, 2011a). The minimum amount of DOPE required for maintaining an acceptable sonosensitivity in vitro, however, was not explored.…”

“…DXR was remote loaded into liposomes using an ammonium sulfate transmembrane gradient (Haran et al, 1993), as previously described by Evjen et al, 2011a. The resulting nominal lipid and DXR concentrations were 16 mg/ml and 1 mg/ml, respectively.…”

“…Liposomes with different mol % of the lipids DOPE, DSPC, DSPE-PEG and cholesterol were prepared by the thin film hydration and sequential extrusion method similarly as previously described (Evjen et al, 2011a The mean target size of the liposomes was 85 ± 5 nm.…”

“…"! found that liposomes based on DOPE as the main phospholipid constituent displayed markedly improved sonosensitivity than DSPE-based liposomes (Evjen et al, 2011a). These DOPE-based liposomes, however, were not evaluated and optimized as drug carriers for in vivo applications.…”

“…(standard liposomal DXR) during in vitro exposure to US Evjen et al, 2011a;Evjen et al, 2011b). An US enhanced therapeutic activity of DSPE-based liposomal DXR was demonstrated in tumoured mice (Hagtvet et al, 2010).…”