Thrombolytic efficacy and cavitation activity of rt-PA echogenic liposomes versus Definity exposed to 120-kHz ultrasound

Abstract

Echogenic liposomes can be used as a vector for co-encapsulation of the thrombolytic drug rt-PA and microbubbles. These agents can be acoustically activated for localized cavitation-enhanced drug delivery. The objective of our study was to characterize thrombolytic efficacy and sustained cavitation nucleation and activity from rt-PA-loaded echogenic liposomes (t-ELIP). A spectrophotometric method was used to determine the enzymatic activity of rt-PA released from t-ELIP and compared to unencapsulated rt-PA. The thrombolytic efficacy of t-ELIP, rt-PA alone, or rt-PA and the commercial contrast agent Definity® exposed to sub-megahertz ultrasound was determined in an in vitro flow model. Ultraharmonic (UH) emissions from stable cavitation were recorded during insonation. Both UH emissions and thrombolytic efficacy were significantly greater for rt-PA and Definity® over either rt-PA alone or t-ELIP with equivalent rt-PA loading. Furthermore, the enzymatic activity of t-ELIP was significantly lower than free rt-PA. When the dosage of t-ELIP was adjusted to compensate for the lack of enzymatic activity, similar thrombolytic efficacy was found for t-ELIP and Definity® and rt-PA. However, sustained ultraharmonic emissions were not observed for t-ELIP in the flow phantom.