Ultrasound-mediated destabilization and drug release from liposomes comprising dioleoylphosphatidylethanolamine.
Novel sonosensitive doxorubicin-containing liposomes comprising dioleoylphosphatidylethanolamine (DOPE) as the main lipid constituent were developed and characterized in terms of ultrasound-mediated drug release in vitro. The liposome formulation showed high sonosensitivity; where approximately 95% doxorubicin was released from liposomes after 6min of 40kHz US exposure in buffered sucrose solution. This represented a 30% increase in release extent in absolute terms compared to liposomes comprising the saturated lipid analogue distearoylphosphatidylethanolamine (DSPE), and a 9-fold improvement in release extent when compared to standard pegylated liposomal doxorubicin, respectively. Ultrasound release experiments in the presence of serum showed a significantly reduction in sonosensitivity of DSPE-based liposomes, whilst the release properties of DOPE-based liposomes were essentially maintained. Dynamic light scattering measurements and cryo-transmission electron microscopy of DOPE-based liposomes after ultrasound treatment indicated liposome disruption and formation of various lipid structures, corroborating the high release extent. The results point to the potential of DOPE-based liposomes as a new class of drug carriers for ultrasound-mediated drug delivery.
Epitarget AS, Oslo, Norway.
Tove J
TJ
Evjen
Esben A
EA
Nilssen
Sabine
S
Barnert
Rolf
R
Schubert
Martin
M
Brandl
Sigrid L
SL
Fossheim
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers; D008081:Liposomes / Q000378:metabolism* / Q000648:ultrastructure*; D008956:Models, Chemical; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols; D014465:Ultrasonics
C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; C094877:dioleoyl phosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin