Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model
Journal of Controlled Release
Drug delivery; Liposome; MR-HIFU; Vx2 tumor model
Clinical-grade doxorubicin encapsulated low temperature sensitive liposomes (LTSLs) were combined with a clinical magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) platform to investigate in vivo image-guided drug delivery. Plasma pharmacokinetics were determined in 3 rabbits. Fifteen rabbits with Vx2 tumors within superficial thigh muscle were randomly assigned into three treatment groups: 1) free doxorubicin, 2) LTSL and 3) LTSL + MR-HIFU. For the LTSL + MR-HIFU group, mild hyperthermia (40-41 °C) was applied to the tumors using an MR-HIFU system. Image-guided non-invasive hyperthermia was applied for a total of 30 min, completed within 1 h after LTSL infusion. High-pressure liquid chromatography (HPLC) analysis of the harvested tumor and organ/tissue homogenates was performed to determine doxorubicin concentration. Fluorescence microscopy was performed to determine doxorubicin spatial distribution in the tumors. Sonication of Vx2 tumors resulted in accurate (mean = 40.5 ± 0.1 °C) and spatially homogenous (SD = 1.0 °C) temperature control in the target region. LTSL + MR-HIFU resulted in significantly higher tumor doxorubicin concentrations (7.6- and 3.4-fold greater compared to free doxorubicin and LTSL respectively, p < 0.05, Newman-Keuls). This improved tumor concentration was achieved despite heating < 25% of the tumor volume. Free doxorubicin and LTSL treatments appeared to deliver more drug in the tumor periphery as compared to the tumor core. In contrast, LTSL + MR-HIFU treatment suggested an improved distribution with doxorubicin found in both the tumor periphery and core. Doxorubicin bio-distribution in non-tumor organs/tissues was fairly similar between treatment groups. This technique has potential for clinical translation as an image-guided method to deliver drug to a solid tumor. © 2011 Elsevier B.V. All rights reserved.
Ranjan, A., Jacobs, G., Woods, D., Negussie, A., Partanen, A., Yarmolenko, P., Gacchina, C., Sharma, K., Frenkel, V., Wood, B., & Dreher, M. (2012). Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model. Journal of Controlled Release, 158 (3). http://dx.doi.org/10.1016/j.jconrel.2011.12.011