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Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound.

Publication ,  Journal Article
Negussie, AH; Yarmolenko, PS; Partanen, A; Ranjan, A; Jacobs, G; Woods, D; Bryant, H; Thomasson, D; Dewhirst, MW; Wood, BJ; Dreher, MR
Published in: Int J Hyperthermia
2011

PURPOSE: Objectives of this study were to: 1) develop iLTSL, a low temperature sensitive liposome co-loaded with an MRI contrast agent (ProHance® Gd-HP-DO3A) and doxorubicin, 2) characterise doxorubicin and Gd-HP-DO3A release from iLTSL and 3) investigate the ability of magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) to induce and monitor iLTSL content release in phantoms and in vivo. METHODS: iLTSL was passively loaded with Gd-HP-DO3A and actively loaded with doxorubicin. Doxorubicin and Gd-HP-DO3A release was quantified by fluorescence and spectroscopic techniques, respectively. Release with MR-HIFU was examined in tissue-mimicking phantoms containing iLTSL and in a VX2 rabbit tumour model. RESULTS: iLTSL demonstrated consistent size and doxorubicin release kinetics after storage at 4°C for 7 days. Release of doxorubicin and Gd-HP-DO3A from iLTSL was minimal at 37°C but fast when heated to 41.3°C. The magnitude of release was not significantly different between doxorubicin and Gd-HP-DO3A over 10 min in HEPES buffer and plasma at 37°, 40° and 41.3°C (p > 0.05). Relaxivity of iLTSL increased significantly (p < 0.0001) from 1.95 ± 0.05 to 4.01 ± 0.1 mMs⁻¹ when heated above the transition temperature. Signal increase corresponded spatially and temporally to MR-HIFU-heated locations in phantoms. Signal increase was also observed in vivo after iLTSL injection and after each 10-min heating (41°C), with greatest increase in the heated tumour region. CONCLUSION: An MR imageable liposome formulation co-loaded with doxorubicin and an MR contrast agent was developed. Stability, imageability, and MR-HIFU monitoring and control of content release suggest that MR-HIFU combined with iLTSL may enable real-time monitoring and spatial control of content release.

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Published In

Int J Hyperthermia

DOI

EISSN

1464-5157

Publication Date

2011

Volume

27

Issue

2

Start / End Page

140 / 155

Location

England

Related Subject Headings

  • Ultrasonography, Interventional
  • Rabbits
  • Phantoms, Imaging
  • Organometallic Compounds
  • Oncology & Carcinogenesis
  • Magnetic Resonance Imaging, Interventional
  • Magnetic Resonance Imaging
  • Liposomes
  • Kinetics
  • Humans
 

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Negussie, A. H., Yarmolenko, P. S., Partanen, A., Ranjan, A., Jacobs, G., Woods, D., … Dreher, M. R. (2011). Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound. Int J Hyperthermia, 27(2), 140–155. https://doi.org/10.3109/02656736.2010.528140
Negussie, Ayele H., Pavel S. Yarmolenko, Ari Partanen, Ashish Ranjan, Genevieve Jacobs, David Woods, Henry Bryant, et al. “Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound.Int J Hyperthermia 27, no. 2 (2011): 140–55. https://doi.org/10.3109/02656736.2010.528140.
Negussie AH, Yarmolenko PS, Partanen A, Ranjan A, Jacobs G, Woods D, et al. Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound. Int J Hyperthermia. 2011;27(2):140–55.
Negussie, Ayele H., et al. “Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound.Int J Hyperthermia, vol. 27, no. 2, 2011, pp. 140–55. Pubmed, doi:10.3109/02656736.2010.528140.
Negussie AH, Yarmolenko PS, Partanen A, Ranjan A, Jacobs G, Woods D, Bryant H, Thomasson D, Dewhirst MW, Wood BJ, Dreher MR. Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound. Int J Hyperthermia. 2011;27(2):140–155.

Published In

Int J Hyperthermia

DOI

EISSN

1464-5157

Publication Date

2011

Volume

27

Issue

2

Start / End Page

140 / 155

Location

England

Related Subject Headings

  • Ultrasonography, Interventional
  • Rabbits
  • Phantoms, Imaging
  • Organometallic Compounds
  • Oncology & Carcinogenesis
  • Magnetic Resonance Imaging, Interventional
  • Magnetic Resonance Imaging
  • Liposomes
  • Kinetics
  • Humans