title: Preservation of imaging capability in sensitive ultrasound contrast agents after indirect plasma sterilization.
abstract: Many injectables are not amenable to standard sterilization methods, which destroy sensitive materials. This is particularly true for ultrasound contrast agents (UCA) consisting of gas bubbles stabilized by a surfactant or polymer shell. We investigated a new method to achieve safe and effective sterilization in production by introducing dielectric-barrier discharge non-thermal plasma. A dielectric-barrier discharge was generated to first produce plasma-treated phosphate-buffered saline (PTPBS), which was used as a sterilant solution for our UCA SE61, avoiding direct heat, pressure, chemicals, or radiation. Treated samples were tested for acoustic properties in vitro and in a flow phantom, and for sterility by standard methods. Three minutes plasma treatment of phosphate-buffered saline (PBS) proved effective. The samples showed significant inactivation of inoculated bacteria upon PTPBS treatment as compared to un-treated-PBS (p=0.0022). The treated and untreated samples showed no statistical significance (p>0.05) in acoustic response or bubble diameter (mean±SEM: 2.52±0.31 μm). Nile Red was used to model intercalation of drug in the hydrophobic shell, intercalated successfully into SE61, and was unaffected by plasma treatment. The PTPBS completely sterilized suspensions of UCA, and it did not compromise the acoustic properties of the agent or its ability to retain a hydrophobic compound.
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Albala
authors.affiliation: Department of Biomedical Engineering, Izmir Katip Celebi University, Izmir, Turkey.
authors.forename: Utku K
authors.initials: UK
authors.lastname: Ercan
authors.affiliation: Center for Surgical Infection and Biofilm, Department of Microbiology & Immunology, College of Medicine, Drexel University, Philadelphia, PA 19102, USA.
authors.forename: Suresh G
authors.initials: SG
authors.lastname: Joshi
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Eisenbrey
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
authors.forename: Nutte
authors.initials: N
authors.lastname: Teraphongphom
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Wheatley
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007267:Injections / Q000379:methods; D011108:Polymers / Q000737:chemistry*; D013242:Sterilization; D014463:Ultrasonography / Q000379:methods
chemical_list: D003287:Contrast Media; D011108:Polymers
keywords: Microbubble; Nonthermal plasma; Sterilization; Surfactant; Ultrasound contrast agents