Preparation and characterization of vesicular nanocarriers: different approaches to brain delivery

The blood–brain barrier (BBB) represents a quite insurmountable hurdle to the delivery of bio-active substances to the central nervous system. The tight junctions between the BBB cells prevent most compounds from entering brain tissue and only the 2% of small polar molecules is able to cross the BBB and, for this reason, the use of a lot of therapeutic agents for treating brain diseases has been limited.1 The development of nanovesicular carriers able to go beyond this barrier is a promising approach to overcome problems related to the delivery of drugs to the brain. In particular, nanovesicles obtained by polysorbate 20 (Tween 20) could be useful because, in vivo, apolipoprotein E (apo E) or B (apo B) adsorb on their surface and this can promote the interaction with the LDL receptor followed by endocytotic uptake by BBB. To reach the brain, an alternative route of administration can be proposed, such as the intranasal delivery («nose to brain»). One of the major problems associated with nasal administration is the rapid removal of drugs or drug delivery systems by mucociliary clearance. This problem could be solved by coating nanocarriers with mucoadhesive agent (NioN 1, Nanobubbles A1, Nanobubbles B1). Furthermore, an alternative strategy is the temporary disruption of the BBB to enhance the possibility of the carrier to reach the brain. The circulating nanobubbles (vesicular systems loaded by a gas as contrast agent) could be able to produce a temporary BBB opening through the widening of tight junctions and the activation of transcellular transport mechanisms, with little effect on the surrounding parenchyma. The aim of this project is the preparation and the characterization of different vesicular systems able, through different mechanisms, to reach the brain