**Abstract**

Successful clinical treatment outcomes rely on achieving optimal systemic delivery of therapeutics. The oral route of administering Active Pharmaceutical Ingredients (API) remains formidable because of ease to the patient and convenience. Yet, the gastrointestinal tract (GIT) poses several barriers that need to be surmounted prior to systemic availability, especially for Class IV type drugs. Drug delivery systems in the form of nanoparticles (NP), can be appropriately formulated to alter the physicochemical properties of APIs, thereby addressing constraints related to absorption from the GIT. Polymers offer amenability in the fabrication of NP due to their diversity. Chitosan has emerged as a strong contender in orally deliverable NP because it is biocompatible, biodegradable and muco-adhesive. Due to the positively charged amine moieties within chitosan (NH3 + ), interactions with the negatively charged sialic acid of mucin within the mucosa is possible, which favors delayed GI transit and epithelial uptake. This ultimately results in improved systemic bioavailability. Thus, we expect research in the use of chitosan in oral NP delivery to intensify as we transcend the frontier toward clinical testing of viable formulations.

**Keywords:** chitosan, gastrointestinal, cellular uptake, nanoparticles, drug delivery, formulation
