Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice: Theranostic contrast agent loaded with nitric oxide
2015 (English)In: Drug Design, Development and Therapy, ISSN 1177-8881, E-ISSN 1177-8881, Vol. 9, 2409-2419 p.Article in journal (Refereed) Published
The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications, i.e. theranostics, of myocardial ischemia. We used gas filled MBs with an average diameter of 4 µm stabilized by a biocompatible shell of poly(vinyl)alcohol. In vitro acoustic tests showed a sufficient enhancement of the backscattered power (20 dB) acquired from the MBs suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1517 m/s) were comparable to those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared to clinically approved contrast agents with fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal 36 min. The application of high power ultrasound pulse (MI=1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 min in air saturated solution and from 17 to 10 min in degased solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6 to 8 hours. This is suitable time for initial diagnostics, treatment and monitoring of the therapeutic effect using single injection of the proposed multifunctional MBs.
Place, publisher, year, edition, pages
2015. Vol. 9, 2409-2419 p.
Medical Equipment Engineering Medical Materials
IdentifiersURN: urn:nbn:se:kth:diva-159765DOI: 10.2147/DDDT.S77790ISI: 000353631900001ScopusID: 2-s2.0-84929178166OAI: oai:DiVA.org:kth-159765DiVA: diva2:787408
QC 20150807. Updated from accepted to published.2015-02-102015-02-102015-08-07Bibliographically approved