A recently developed ultrasound contrast agent, rt-PA-loaded echogenic liposomes (TELIP), was assessed in vitro using a clinical diagnostic ultrasound scanner (Philips HDI 5000) equipped with a linear array (L12-5). The stability and echogenicity of static TELIP suspensions were determined using 4.5-MHz harmonic B-mode pulses (Pr=120 kPa; MI=0.04) in an anechoic chamber. An in vitro flow phantom with a flow rate of 5 ml/min at 37 °C was also used to assess TELIP for ultrasonically-triggered drug release. TELIP samples were exposed to: (1) Fundamental 6.9-MHz B-mode pulses (Pr=600 kPa; MI=0.04) where diffusion of gas out of the liposomes occurs over 60 min, or (2) 6.0-MHz color Doppler pulses (PD=3.33 μs, PRF=1 kHz) at two exposure levels, 0.8 MPa (MI=0.22) for which acoustically driven diffusion was evident or 2.6 MPa (MI=0.7), for which rapid fragmentation was confirmed. Exposure of TELIP to Triton-X, a nonionic detergent, served as a positive control for drug release. Release of rt-PA for each ultrasound exposure protocol was assayed spectrophotometrically (Shimadzu UV-1700). The thrombolytic drug remained associated with the lipid bilayer when exposed to B-mode pulses over time and was released when exposed to color Doppler pulses. [This work was supported by NIH 1RO1 NS047603 and NIH 1R01 HL074002.]
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Smith et al. (2007) studied this question.