Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: An in vivo proof-of-concept study

Temperature-sensitive liposomes (TSLs) co-encapsulating doxorubicin and 250 mM [Gd(HPDO3A)(H 2O)] were evaluated for HIFU-mediated drug delivery under MR image guidance. In vitro studies showed simultaneous and quantitative release of the drug and the MRI contrast agent from the lumen of the TSLs at...

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Bibliographic Details
Published in:Journal of controlled release 2011-02, Vol.150 (1), p.102-110
Main Authors: de Smet, Mariska, Heijman, Edwin, Langereis, Sander, Hijnen, Nicole M., Grüll, Holger
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacokinetics
Biological and medical sciences
Contrast agents
Contrast Media - administration & dosage
Contrast Media - pharmacokinetics
doxorubicin
Doxorubicin - administration & dosage
Doxorubicin - pharmacokinetics
Drug delivery
Focused ultrasound
Gadolinium
General pharmacology
Heterocyclic Compounds - administration & dosage
Heterocyclic Compounds - pharmacokinetics
Hyperthermia
Image guidance
in vitro studies
Liposomes - chemistry
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Medical sciences
Nanomedicine
neoplasms
Neoplasms - diagnostic imaging
Neoplasms - drug therapy
Oncology
Organometallic Compounds - administration & dosage
Organometallic Compounds - pharmacokinetics
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Rats
Temperature
Temperature-sensitive liposome
Ultrasonics
Ultrasonography
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Summary:Temperature-sensitive liposomes (TSLs) co-encapsulating doxorubicin and 250 mM [Gd(HPDO3A)(H 2O)] were evaluated for HIFU-mediated drug delivery under MR image guidance. In vitro studies showed simultaneous and quantitative release of the drug and the MRI contrast agent from the lumen of the TSLs at 42 °C, while no leakage was observed over 1 h at 37 °C. In a proof-of-concept study, local hyperthermia has been applied for 30 min in 9L rat tumors using a clinical MR-HIFU system. The local temperature-triggered release of [Gd(HPDO3A)(H 2O)] was monitored with interleaved T 1 mapping of the tumor tissue. A good correlation between the ΔR 1, the uptake of doxorubicin and the gadolinium concentration in the tumor was found, implying that the in vivo release of doxorubicin from TSLs can be probed in situ with the longitudinal relaxation time of the co-released MRI contrast agent. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2010.10.036