Localized ultrasound enhances delivery of rapamycin from microbubbles to prevent smooth muscle proliferation

JOURNAL OF CONTROLLED RELEASE

卷:154

Article

Phillips, Linsey C.¹  Klibanov, Alexander L.²  Wamhoff, Brian R.^2,3  Hossack, John A.¹ 

[1] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA

[2] Univ Virginia, Dept Med, Div Cardiovasc, Charlottesville, VA 22908 USA

[3] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

关键词: Ultrasound contrast agents;    Microbubbles;    Drug delivery;    Smooth muscle cells;    Rapamycin;   

DOI  :  10.1016/j.jconrel.2011.04.020

来源: Elsevier

【 摘 要 】

Microbubble contrast agents have been shown to enhance reagent delivery when activated by ultrasound. We hypothesized that ultrasound would enhance delivery of rapamycin, an antiproliferative agent, from the shell of microbubbles, thus reducing proliferation of vascular smooth muscle cells. Our objective was to determine optimal ultrasound parameters that maximized therapeutic efficacy, maintained cell adherence, and minimized the drug exposure time. In vitro assays determined that ultrasound (1 MHz, 0.5% duty cycle) is required to successfully deliver rapamycin from microbubbles and reduce proliferation. Co-injection of rapamycin with control microbubbles did not result in a reduction in proliferation. Successful reduction in proliferation (>50%) required pulses at least 10 cycles in length and at least 300 kPa peak negative pressure at which point 90% of cells remained adherent. The anti-proliferative effect was also localized within a 6 mm wide zone by focusing the ultrasound beam. (c) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

Free