ULTRASOUND-ACTIVATED OXYGEN-LOADED NANOBUBBLES AS THERAPEUTIC TOOLS AGAINST HYPOXIA

Aiming at developing effective, almost non-invasive and low-cost nanotechnological devices to treat a variety of hypoxia-related dermal diseases, including bedsores and diabetic foot, in the present work different formulations of oxygen-loaded nanobubbles (OLNs) were developed. OLNs were constituted by a shell of biocompatible and biodegradable polysaccharide (chitosan), and an O2-containing core with two alternative fluorocarbons, namely decafluoropentane (DFP; boiling point: 51°C) or perfluoropentane (PFP; boiling point: 30°C). OLNs were dissolved both in liquid (water) or in gel (hydroxyethylcellulose) formulations, with the latter being more suitable for skin spreading. After characterization of their physical-chemical properties, OLN abilities to deliver O2 with or without activation by ultrasounds (US) were investigated. In vitro, O2 release from OLNs was firstly monitored up to 350 min through Hach Langhe LDO oxymeter; thereafter, OLN abilities to deliver O2 through natural membranes (pig ear skin) after activation by US were evaluated. In vivo, O2 release through small portions of shaved mouse skin treated with OLNs and US was monitored up to 15 min through TINA TCM30 oxymeter. Results from both in vitro and in vivo experiments showed that OLNs, either in liquid or in gel formulations, promoted a significant and sustained increase of O2 concentration, with DFP-containing OLNs being more effective in inducing O2 release than those with PFP; additionally, US promoted O2 delivery through skin membranes. In conclusion, US-activated OLNs proved to be effective in overcoming dermal membranes and in providing tissues with O2. Therefore, they appear promising tools for topical treatment of superficial hypoxic lesions.