Chitosan-based nanomedicines: A review of the main challenges for translating the science of polyelectrolyte complexation into innovative pharmaceutical products

Chitosan (CS) is a versatile biopolymer used in the fabrication of different types of drug delivery systems. It is recognized mainly by its pH-responsive behavior, mucoadhesive, and membrane permeation enhancer properties, which can be explored for modulated drug release and localized delivery. Other biological properties (immune adjuvant, and antitumoral) put this biopolymer at the forefront of raw materials for manufacturing new multifunctional products. Their material attributes can be improved by chemical modification, resulting in CSbased derivatives with controlled hydrophobicity, better solubility, and higher bio(mucoadhesive) capacity. The resultant CS-based materials have been used to fabricate nanoparticles (CS NPs) for the delivery of small molecules and macromolecules into body tissues. Despite many studies that have reported the efficacy and safety of CS NPs, there are still some important issues to be considered before they reach the market. Herein, we demonstrate the perceived risks of using CS NPs can be partially explained by some important gaps in basic science, technological processes, and aspects related to quality control and regulatory affairs. This review discusses the challenges and possible solutions for each of the above-mentioned points with the perspective of enabling CS NPs as technological platforms for the pharmaceutical industry.