Polysaccharides nanobubbles as a versatile tool for biomedical applications

Roberta CAVALLI, Università degli Studi di Torino

Nanobubbles are bubbles with sizes in the nanometer order of magnitude. These nanoscale systems were originally designed as contrast agents, being efficient reflectors of ultrasound (US) energy. More recently, they have been studied in relation to drug, gene and gas delivery. Nanobubbles can be considered US responsive nanocarriers with improved stability and longer residence time in the systemic circulation compared to microbubbles. Moreover, they have the possibility of extravasation from the blood vessels into the surrounding tissues, improving delivery efficiency and localisation. They are spherical core-shell nanostructure filled with a gas or a low boiling point compound. Polysaccharide nanobubbles comprise a perfluorocarbon core and a polymer-based shell consisting of polysaccharides, such as chitosan, agarose and dextran derivatives. They have been designed using safe, biocompatible, biodegradable and regulatory admitted components. Generally, the core is constituted of perfluoropentane or decafluoropentane, liquid at room temperature, to exploit a simple preparation set-up, if compared with the use of gases. The  action of therapeutic US, by means of a mechanism called acoustic droplet vaporization (ADV), can convert perfluorocarbon nanodroplets into nano-microbubbles.

Polysaccharide nanobubbles have been exploited as a platform for the delivery of bioactive molecules by various administration routes. Three main loading types are possible. Drugs might be encapsulated within the core, otherwise, might be incorporated within or just beneath the nanobubble shell. This versatile structure can permit the co-loading for combination delivery.

A broad variety of nanobubble applications have been studied, comprising nucleic acids delivery for improving transfection efficiency and oxygen release for hypoxia prevention and treatment.

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