Objectives. Oxygen-Loaded Nanobubbles (OLNs) are innovative oxygenating drugs aimed at treating hypoxia-associated pathologies, including cancer, pre-eclampsia, and chronic wounds. In the present work, a new OLN formulation was developed, and OLNs were characterized for size, surface charge, O2 content or release ability, and cellular cytotoxicity. Methods. Dextran-shelled and decafluoropentane-containing OLNs were solved in phosphate buffer saline (PBS) solution. OLN sizes and charges were characterized in vitro by optical microscopy and light scattering; O2 release was measured through a pulse oxymeter; and OLN cytotoxicity was tested on human dermal microvascular endothelial cells (HMEC-1 cell line), human monocytes isolated from peripheral blood (primary cell cultures), and murine alveolar macrophages (MH-S cell line) by lactate dehydrogenase spectrometric assay. Results. OLNs displayed ~500 nm diameters and negatively charged surfaces. As emerged from comparison with O2-Saturated Solution (OSS, positive control), OLNs showed an effective and time-sustained ability to deliver O2. Finally, no toxic effects up to 24-48 h were observed in human and murine cells, cultured in normoxic and in hypoxic conditions. Conclusions. Dextran-shelled, decafluoropentane-containing OLNs appear to be low-cost, easy-to-be-made, effective, and safe oxygenating drugs. Further in vivo studies will clarify their therapeutic potential in hypoxia-associated diseases.
In vitro characterization of new dextran-shelled, decafluoropentane-containing Oxygen-Loaded Nanobubbles.
PRATO, Mauro;GAZZANO, Elena;GULINO, GIULIA ROSSANA;GIRIBALDI, Giuliana;GUIOT, Caterina
2013-01-01
Abstract
Objectives. Oxygen-Loaded Nanobubbles (OLNs) are innovative oxygenating drugs aimed at treating hypoxia-associated pathologies, including cancer, pre-eclampsia, and chronic wounds. In the present work, a new OLN formulation was developed, and OLNs were characterized for size, surface charge, O2 content or release ability, and cellular cytotoxicity. Methods. Dextran-shelled and decafluoropentane-containing OLNs were solved in phosphate buffer saline (PBS) solution. OLN sizes and charges were characterized in vitro by optical microscopy and light scattering; O2 release was measured through a pulse oxymeter; and OLN cytotoxicity was tested on human dermal microvascular endothelial cells (HMEC-1 cell line), human monocytes isolated from peripheral blood (primary cell cultures), and murine alveolar macrophages (MH-S cell line) by lactate dehydrogenase spectrometric assay. Results. OLNs displayed ~500 nm diameters and negatively charged surfaces. As emerged from comparison with O2-Saturated Solution (OSS, positive control), OLNs showed an effective and time-sustained ability to deliver O2. Finally, no toxic effects up to 24-48 h were observed in human and murine cells, cultured in normoxic and in hypoxic conditions. Conclusions. Dextran-shelled, decafluoropentane-containing OLNs appear to be low-cost, easy-to-be-made, effective, and safe oxygenating drugs. Further in vivo studies will clarify their therapeutic potential in hypoxia-associated diseases.
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