TY - JOUR
T1 - Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia
AU - Li, Li
AU - ten Hagen, Timo L.M.
AU - Schipper, Debby
AU - Wijnberg, Tom M.
AU - van Rhoon, Gerard C.
AU - Eggermont, Alexander M.M.
AU - Lindner, Lars H.
AU - Koning, Gerben A.
N1 - Funding Information:
The authors thank Dr. Kristina Djanashvili, Dr. Daniel Schuhle, Dr. Aurelie M. A. Brizard at ChemTech, Delft University of Technology, Delft, for DSC measurements; Dr. Martin Hossann at Medical Clinic and Pre-clinic III, Ludwig-Maximilians University, Munich, and Dr. Gert van Cappellen at Erasmus MC, Rotterdam, for technical support; Stichting Vanderes , Stichting Fondsen , SEHK , Dr. Mildred Scheel Stiftung and Erasmus MC grants (Mrace) for financial support.
PY - 2010/4
Y1 - 2010/4
N2 - Liposomes are potent nanocarriers to deliver chemotherapeutic drugs to tumors. However, the inefficient drug release hinders their application. Thermosensitive liposomes (TSL) can release drugs upon heat. This study aims to identify the optimum 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG2000) concentration in stealth TSL to improve content release efficiency under mild hyperthermia (HT). TSL were prepared with DSPE-PEG2000 from 1 to 10mol%, around 80nm in size. Quenched carboxyfluorescein (CF) in aqueous phase represented encapsulated drugs. In vitro temperature/time-dependent CF release and TSL stability in serum were quantified by fluorometry. In vivo CF release in dorsal skin flap window chamber models implanted with human BLM melanoma was captured by confocal microscopy. In vitro heat triggered CF release increased with increasing DSPE-PEG2000 density. However, 6mol% and higher DSPE-PEG2000 caused CF leakage at physiological temperature. TSL with 5mol% DSPE-PEG2000 were stable at 37°C, while released 60% CF in 1min and almost 100% CF in 1h at 42°C. In vivo optical intravital imaging showed immediate massive CF release above 41°C. In conclusion, incorporation of 5mol% DSPE-PEG2000 optimized stealth TSL content release triggered by HT.
AB - Liposomes are potent nanocarriers to deliver chemotherapeutic drugs to tumors. However, the inefficient drug release hinders their application. Thermosensitive liposomes (TSL) can release drugs upon heat. This study aims to identify the optimum 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG2000) concentration in stealth TSL to improve content release efficiency under mild hyperthermia (HT). TSL were prepared with DSPE-PEG2000 from 1 to 10mol%, around 80nm in size. Quenched carboxyfluorescein (CF) in aqueous phase represented encapsulated drugs. In vitro temperature/time-dependent CF release and TSL stability in serum were quantified by fluorometry. In vivo CF release in dorsal skin flap window chamber models implanted with human BLM melanoma was captured by confocal microscopy. In vitro heat triggered CF release increased with increasing DSPE-PEG2000 density. However, 6mol% and higher DSPE-PEG2000 caused CF leakage at physiological temperature. TSL with 5mol% DSPE-PEG2000 were stable at 37°C, while released 60% CF in 1min and almost 100% CF in 1h at 42°C. In vivo optical intravital imaging showed immediate massive CF release above 41°C. In conclusion, incorporation of 5mol% DSPE-PEG2000 optimized stealth TSL content release triggered by HT.
KW - Drug delivery
KW - Hyperthermia
KW - Intravital microscopy
KW - Poly(ethylene glycol)
KW - Thermosensitive liposomes
KW - Triggered release
KW - Tumor
UR - http://www.scopus.com/inward/record.url?scp=77950338359&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2010.01.006
DO - 10.1016/j.jconrel.2010.01.006
M3 - Article
C2 - 20074595
AN - SCOPUS:77950338359
SN - 0168-3659
VL - 143
SP - 274
EP - 279
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -