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Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice.
Grishenkov, Dmitry; Gonon, Adrian; Weitzberg, Eddie; Lundberg, Jon O; Harmark, Johan; Cerroni, Barbara; Paradossi, Gaio; Janerot-Sjoberg, Birgitta.
Afiliación
  • Grishenkov D; Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden ; Department of Medical Engineering, KTH, Royal Institute of Technology, School of Technology and Health, Stockholm, Sweden ; Department of Clinical Physiology, Karolinska University Hospital, Stoc
  • Gonon A; Department of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden ; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Weitzberg E; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • Lundberg JO; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • Harmark J; Department of Biosciences and Nutrition, Karolinska Institutet, KTH, Royal Institute of Technology, School of Technology and Health, Stockholm, Sweden.
  • Cerroni B; Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy.
  • Paradossi G; Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy.
  • Janerot-Sjoberg B; Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden ; Department of Medical Engineering, KTH, Royal Institute of Technology, School of Technology and Health, Stockholm, Sweden ; Department of Clinical Physiology, Karolinska University Hospital, Stoc
Drug Des Devel Ther ; 9: 2409-19, 2015.
Article en En | MEDLINE | ID: mdl-25995614
The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications (ie, theranostics) of myocardial ischemia. We used gas-filled MBs with an average diameter of 4 µm stabilized by a biocompatible shell of polyvinyl alcohol. In vitro acoustic tests showed 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 (1,517 m/s) were comparable with those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared with clinically approved contrast agents with a 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 to 36 minutes. The application of high-power ultrasound pulse (mechanical index =1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 minutes in air-saturated solution and from 17 to 10 minutes in degassed solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6-8 hours. This is a suitable time for initial diagnostics, treatment, and monitoring of the therapeutic effect using a single injection of the proposed multifunctional MBs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ultrasonido / Medios de Contraste / Nanomedicina Teranóstica / Óxido Nítrico Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Drug Des Devel Ther Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2015 Tipo del documento: Article Pais de publicación: Nueva Zelanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ultrasonido / Medios de Contraste / Nanomedicina Teranóstica / Óxido Nítrico Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Drug Des Devel Ther Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2015 Tipo del documento: Article Pais de publicación: Nueva Zelanda