Preparation and characterization of dextran nanobubbles for oxygen delivery

• Published in: International journal of pharmaceutics Vol. 381; no. 2; pp. 160 - 165
• Main Authors: Cavalli, R., Bisazza, A., Giustetto, P., Civra, A., Lembo, D., Trotta, G., Guiot, C., Trotta, M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 03-11-2009
• Subjects: Animals; Cell Hypoxia; Cell Survival - drug effects; Cercopithecus aethiops; Dextran; Dextrans - adverse effects; Dextrans - chemistry; Dextrans - pharmacology; Drug Delivery Systems - methods; Drug Stability; Endocytosis; Excipients - chemistry; Fluorocarbons - adverse effects; Fluorocarbons - chemistry; Fluorocarbons - pharmacology; Hemolysis - drug effects; Hemolytic Agents - adverse effects; Hemolytic Agents - chemistry; Hemolytic Agents - pharmacology; Humans; Hypoxia; Hypoxia - therapy; Microbubbles - adverse effects; Nanobubbles; Nanostructures - administration & dosage; Nanostructures - chemistry; Nanostructures - ultrastructure; Nephelometry and Turbidimetry; Oxygen - administration & dosage; Oxygen - analysis; Oxygen delivery; Plasma - chemistry; Povidone - chemistry; Rats; Sodium Chloride - chemistry; Sonication; Surface Properties; Time Factors; Ultrasound; Vero Cells; Dextran; Hypoxia; Nanobubbles; Oxygen delivery; Ultrasound
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2009.07.010

Dextran nanobubbles were prepared with a dextran shell and a perfluoropentan core in which oxygen was stored. To increase the stability polyvinylpirrolidone was also added to the formulation as stabilizing agent. Rhodamine B was used as fluorescent marker to obtain fluorescent nanobubbles. The nanobubble formulations showed sizes of about 500
nm, a negative surface charge and a good capacity of loading oxygen, no hemolytic activity or toxic effect on cell lines. The fluorescent labelled nanobubbles could be internalized in Vero cells. Oxygen-filled nanobubbles were able to release oxygen in different hypoxic solutions at different time after their preparation in
in vitro experiments. The oxygen release kinetics could be enhanced after nanobubble insonation with ultrasound at 2.5
MHz. The oxygen-filled nanobubble formulations might be proposed for therapeutic applications in various diseases.