TY - JOUR
T1 - Determination of platinum drug release and liposome stability in human plasma by CE-ICP-MS
AU - Nguyen, Trinh Thi Nhu Tam
AU - Ostergaard, Jesper
AU - Stürup, Stefan
AU - Gammelgaard, Bente
N1 - Copyright © 2013 Elsevier B.V. All rights reserved.
PY - 2013/6/5
Y1 - 2013/6/5
N2 - An in vitro method for simultaneous assessment of platinum release and liposome stability of liposomal formulations in human plasma is demonstrated. The development and assessment of the method was performed on a PEGylated liposomal formulation containing cisplatin. Complete separation of free cisplatin, encapsulated cisplatin and cisplatin bound to plasma components was achieved by capillary electrophoresis (CE) separation and simultaneous monitoring of phosphorous (phospholipid) and platinum (cisplatin) by inductively coupled plasma mass spectrometry (ICP-MS). The method allows assessment of the encapsulation efficiency of the formulation, the physical stability of liposomes as well as cisplatin leakage in human plasma. The method was applied for studying the disintegration of liposomes and the interactions of leaked cisplatin with plasma components. Triggered release of the drug into plasma by sonication was also demonstrated. Analysis of liposomal formulations with alternative phospholipid compositions containing oxaliplatin showed similar results. Thus, the present in vitro method is suitable for mimicking the in vivo drug release profile in human plasma after administration of liposomal platinum formulations to patients. This approach may be of use in early drug development as well as in quality control.
AB - An in vitro method for simultaneous assessment of platinum release and liposome stability of liposomal formulations in human plasma is demonstrated. The development and assessment of the method was performed on a PEGylated liposomal formulation containing cisplatin. Complete separation of free cisplatin, encapsulated cisplatin and cisplatin bound to plasma components was achieved by capillary electrophoresis (CE) separation and simultaneous monitoring of phosphorous (phospholipid) and platinum (cisplatin) by inductively coupled plasma mass spectrometry (ICP-MS). The method allows assessment of the encapsulation efficiency of the formulation, the physical stability of liposomes as well as cisplatin leakage in human plasma. The method was applied for studying the disintegration of liposomes and the interactions of leaked cisplatin with plasma components. Triggered release of the drug into plasma by sonication was also demonstrated. Analysis of liposomal formulations with alternative phospholipid compositions containing oxaliplatin showed similar results. Thus, the present in vitro method is suitable for mimicking the in vivo drug release profile in human plasma after administration of liposomal platinum formulations to patients. This approach may be of use in early drug development as well as in quality control.
U2 - 10.1016/j.ijpharm.2013.03.055
DO - 10.1016/j.ijpharm.2013.03.055
M3 - Journal article
C2 - 23583709
SN - 0378-5173
VL - 449
SP - 95
EP - 102
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -