How can chitosans be used for drug, gene, or vaccine delivery?

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The partly hydrophobic, partly polycationic nature of chitosans make them ideally suited as a carrier for different types of payloads. Chitosan hydrogels can be used for the topical ("on the surface", e.g. on the skin) application of drugs. Nanoformulated chitosans, e.g. nanoscale hydrogels and nanoparticles, but also nano-capsules e.g. with an inner oily core to accommodate highly hydrophobic, water-insoluble drugs, can be used to deliver different payloads directly to cells, as they tend to be taken up easily by human cells. Interestingly, such chitosan nanoformulations appear to be able to penetrate even the blood-brain barrier, allowing to delivery drugs into the brain which is otherwise difficult to target. Also, such chitosan nanoformulations can be modified by grafting e.g. antibodies onto their surfaces to support targeted drug delivery to cells carrying the respective antigens. The most critical aspect of internal drug, gene, or vaccine delivery using chitosan nanoformulations is the unknown metabolic fate of the chitosans upon cellular uptake, as todays chitosans are rather poorly degraded by human enzymes such as chitotriosidase. Here, third-generation designer chitosans with inbuilt cleavage sites might offer a solution in future.