TY - JOUR
T1 - Enhanced in vivo bioluminescence imaging using liposomal luciferin delivery system
AU - Kheirolomoom, Azadeh
AU - Kruse, Dustin E.
AU - Qin, Shengping
AU - Watson, Katherine E.
AU - Lai, Chun Yen
AU - Young, Lawrence J T
AU - Cardiff, Robert D.
AU - Ferrara, Katherine W
PY - 2010/1/25
Y1 - 2010/1/25
N2 - To provide a continuous and prolonged delivery of the substrate D-luciferin for bioluminescence imaging in vivo, luciferin was encapsulated into liposomes using either the pH gradient or acetate gradient method. Under optimum loading conditions, 0.17 mg luciferin was loaded per mg of lipid with 90-95% encapsulation efficiency, where active loading was 6 to 18-fold higher than that obtained with passive loading. Liposomal luciferin in a long-circulating formulation had good shelf stability, with 10% release over 3-month storage at 4 °C. Pharmacokinetic profiles of free and liposomal luciferin were then evaluated in transgenic mice expressing luciferase. In contrast to rapid in vivo clearance of free luciferin (t1/2 = 3.54 min), luciferin encapsulated into long-circulating liposomes showed a prolonged release over 24 h. The first-order release rate constant of luciferin from long-circulating liposomes, as estimated from the best fit of the analytical model to the experimental data, was 0.01 h- 1. Insonation of luciferin-loaded temperature-sensitive liposomes directly injected into one tumor of Met1-luc tumor-bearing mice resulted in immediate emission of light. Systemic injection of luciferin-loaded long-circulating liposomes into Met1-luc tumor-bearing mice, followed by unilateral ultrasound-induced hyperthermia, produced a gradual increase in radiance over time, reaching a peak at 4-7 h post-ultrasound.
AB - To provide a continuous and prolonged delivery of the substrate D-luciferin for bioluminescence imaging in vivo, luciferin was encapsulated into liposomes using either the pH gradient or acetate gradient method. Under optimum loading conditions, 0.17 mg luciferin was loaded per mg of lipid with 90-95% encapsulation efficiency, where active loading was 6 to 18-fold higher than that obtained with passive loading. Liposomal luciferin in a long-circulating formulation had good shelf stability, with 10% release over 3-month storage at 4 °C. Pharmacokinetic profiles of free and liposomal luciferin were then evaluated in transgenic mice expressing luciferase. In contrast to rapid in vivo clearance of free luciferin (t1/2 = 3.54 min), luciferin encapsulated into long-circulating liposomes showed a prolonged release over 24 h. The first-order release rate constant of luciferin from long-circulating liposomes, as estimated from the best fit of the analytical model to the experimental data, was 0.01 h- 1. Insonation of luciferin-loaded temperature-sensitive liposomes directly injected into one tumor of Met1-luc tumor-bearing mice resulted in immediate emission of light. Systemic injection of luciferin-loaded long-circulating liposomes into Met1-luc tumor-bearing mice, followed by unilateral ultrasound-induced hyperthermia, produced a gradual increase in radiance over time, reaching a peak at 4-7 h post-ultrasound.
KW - Active loading
KW - Bioluminescence imaging
KW - D-luciferin
KW - Hyperthermia
KW - Liposome
KW - Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=72149117948&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72149117948&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2009.08.029
DO - 10.1016/j.jconrel.2009.08.029
M3 - Article
C2 - 19748536
AN - SCOPUS:72149117948
VL - 141
SP - 128
EP - 136
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 2
ER -