Chitosan nanocarriers: Pioneering encapsulation and targeted delivery of 5-fluorouracil - A comprehensive review

5-Fluorouracil (5FU) is a common chemotherapy drug for various cancers. It has exhibited large potentials for the treatment of both malignant and premalignant tumors. In the meantime, topical application of 5FU has been limited to surface pre-carcinogenic tumors. So far, a number of nano systems have been developed for encapsulation and targeted delivery of 5FU to improve its solubility, bioavailability, and functional characteristics, leading to the development of, for example, 5FU carriers in topical treatments. Due to their considerable advantages over ordinary therapies, nanotechnology-based drug delivery systems (DDSs), particularly polymeric nanocarriers (PNCs), have led to some sorts of evolution in many fields, including disease diagnosis and DDS. As a naturally occurring polymer, chitosan (CS) has long been regarded because of its biodegradability, biocompatibility, polycationic nature, non-toxicity, and non-allergenic nature. In addition, the pH-responsive nature of CS provides an exact drug dispersion in the cancer environment, converting it a promising carrier system. Utilization of 5-FU into carbon nanocarriers has indicated positive results such as targeted delivery to tumors and prevention of cancer activity. Researchers have successfully synthesized a handful of CS nanocarriers with distinctive characteristics for targeted delivery of 5FU; these come in different forms, including nano-sized particles (NPs), composites (NCs), emulsions (NEs), and fibers (NFs). This study reviews the mechanism of CS in different formulations by analyzing the physicochemical characteristics of the corresponding DDS in terms of morphology, surface charge, release profile, and encapsulation driving force. A more detailed analysis was performed on the most popular pharmaceutical applications of 5FU-loaded CS NPs. Effective facilitation of targeted delivery of 5FU and improvement of its therapeutic effects for various cancers by the CS were also indicated. Herein, the readers are introduced to nanoscale systems based on natural polymers like chitosan as promising platforms for cancer diagnosis and therapy. More recent discoveries on mechanistic anticancer behavior of 5FU-loaded CS NPs was further discussed.