In vitro stability and content release properties of phosphatidylglyceroglycerol containing thermosensitive liposomes.
Recently, we reported that 1,2-dipalmitoyl-sn-glycero-3-phosphoglyceroglycerol (DPPGOG) prolongs the circulation time of thermosensitive liposomes (TSL). Since the only TSL formulation in clinical trials applies DSPE-PEG2000 and lysophosphatidylcholine (P-lyso-PC), the objective of this study was to compare the influence of these lipids with DPPGOG on in vitro stability and heat-induced drug release properties of TSL. The content release rate was significantly increased by incorporating DPPGOG or P-lyso-PC in TSL formulations. DPPC/DSPC/DPPGOG 50:20:30 (m/m) and DPPC/P-lyso-PC/DSPE-PEG2000 90:10:4 (m/m) did not differ significantly in their release rate of carboxyfluorescein with >70% being released within the first 10s at their phase transition temperature. Furthermore, DPPC/DSPC/DPPGOG showed an improved stability at 37 degrees C in serum compared to the PEGylated TSL. The in vitro properties of DPPGOG-containing TSL remained unchanged when encapsulating doxorubicin instead of carboxyfluorescein. The TSL retained 89.1+/-4.0% of doxorubicin over 3 h at 37 degrees C in the presence of serum. The drug was almost completely released within 120s at 42 degrees C. In conclusion, DPPGOG improves the in vitro properties in TSL formulations compared to DSPE-PEG2000, since it not only increases the in vivo half-life, it even increases the content release rate without negative effect on TSL stability at 37 degrees C which has been seen for DSPE-PEG2000/P-lyso-PC containing TSL.
Hossann
Martin
M
Department of Internal Medicine III, Klinikum Grosshadern Medical Center (KGMC), Ludwig-Maximilians University, Munich, Germany.
Wiggenhorn
Michael
M
Schwerdt
Alenka
A
Wachholz
Kirsten
K
Teichert
Nicole
N
Eibl
Hansjörg
H
Issels
Rolf D
RD
Lindner
Lars H
LH
D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004355:Drug Stability; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D010168:Palmitates / Q000737:chemistry*; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D012995:Solubility; D013696:Temperature
C520885:1,2-dipalmitoyl-glycerophosphatidyl-glycerol; D008051:Lipid Bilayers; D008081:Liposomes; D010168:Palmitates; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005990:Glycerol