Ultrasound-mediated oxygen-nanotherapy in superficial tissues.

Tissues hypoxia is a common phenomenon originated by metabolic, ischaemic or infective deseases. Many of such hypoxic regions (e.g. bedsores, diabetic foot…) are located superficially and extra oxygen, properly encapsulated in Oxygen Loaded Nanobubbles (OLNs) could be provided through ultrasonic transdermal sonophoresis. Nanobubbles consist in a shell of biocompatible and biodegradable material (chitosan or dextran) and an oxygen-storing perfluoropentane core (PFP). OLNs can be manufactured in liquid (water) or gel (hydroxyethylcellulose) formulations, with the latter being more suitable for skin spreading. Local sonophoresis throughout natural membranes (pig skin) can be induced by OLNs sonication with a 5 minutes standard procedure (f= 2.5MHz, P=5W). The transdermal O2 release, monitored by measuring the dissolved O2 concentration, is sustained and lasts for longer times than the corresponding O2-saturated formulations. The administration of OLN on both JEG-3 choriocarcinoma cell cultures and small fragments of human chorionic villi incubated in hypoxic conditions dramatically reduces the expression of HIF-1, proving their biological efficacy. OLN sonication, being a non-invasive and low-cost nanotechnological device, is a good candidate to treat hypoxia-related superficial diseases.