Size-tailored natural polysaccharides for advanced drug delivery: From nano to macro

Abstract Natural polysaccharides are valued in drug delivery for their biocompatibility, biodegradability, and low immunogenicity. Many of these polymers, including chitosan, alginate, hyaluronic acid (HA), and pectin (PEC), originate from food-medicine homology resources and have a long history of safe human use. A key advantage of these polymers is their chemical versatility, which allows precise control over molecular assembly and dimensional programmability. This feature enables the construction of carriers ranging from nanoscopic colloids to macroscopic implants. Although polysaccharide-based systems have been intensively studied, most investigations have focused on chemical modifications or encapsulation strategies. The physical size of the carrier has received comparatively less systematic consideration. In this review, we propose a size-tailored classification that organizes polysaccharide delivery platforms into nanoscale, microscale, and macroscale categories, with each defined by its distinct functional role in the delivery process. Nanoscale platforms, including nanoparticles, micelles, and nanogels, are well suited for improving solubility, achieving targeted delivery, and facilitating cellular uptake after intravenous administration. Microscale systems, such as microcapsules, microspheres, and microneedles, act as localized depots that provide sustained release and minimize drug distribution to nontarget tissues. Macroscale constructs, including hydrogels, films, and tablets, accommodate large drug doses and enable site-specific application, often with enhanced patient compliance. By examining how carrier dimensions influence drug transport, tissue retention, and release dynamics, this review establishes size control as a meaningful and accessible design parameter. Therefore, this framework offers a rational basis for engineering next-generation polysaccharide-based delivery systems in the context of precision medicine.