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Chitosan, a natural carbohydrate polymer, has long been investigated for drug delivery and medical applications due to its biodegradability, biocompatibility and low toxicity. The micro/nanoparticulate forms of chitosan are reported to enhance the efficiency of drug delivery with better physicochemical properties including improved solubility and bioavailability. This polymer is known to be biodegradable and biocompatible; however, crosslinked chitosan particles may not be biodegradable. Crosslinkers (e.g., tripolyphosphate and glutaraldehyde) are needed for efficient micro/nanoparticle formation, but it is not clear whether the resultant particles are biodegradable or able to release the encapsulated drug fully. To date, no studies have conclusively demonstrated the complete biodegradation or elimination of chitosan nanoparticles in vivo. Herein we review the synthesis and degradation mechanisms of chitosan …