Ultrasound-mediated destabilization and drug release from liposomes comprising dioleoylphosphatidylethanolamine |
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Authors: | Tove J Evjen Esben A Nilssen Sabine Barnert Rolf Schubert Martin Brandl Sigrid L Fossheim |
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Institution: | 1. Epitarget AS, Oslo, Norway;2. University of Tromsø, Department of Pharmacy, Tromsø, Norway;3. University of Freiburg, Department of Pharmaceutical Technology and Biopharmacy, Freiburg, Germany |
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Abstract: | 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 6 min of 40 kHz 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. |
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