Multifunctional investigation of “drug–excipient unification” of natural polysaccharide nanocarriers: A new paradigm from drug delivery to adjuvant therapy

Abstract

The concept of “drug–excipient unification”involves replacing or reducing traditional excipients with components that possess pharmacological activity, thereby simultaneously enhancing therapeutic efficacy and reducing toxicity. This concept can be effectively implemented in pharmaceutical formulation design. Polysaccharides, as natural biomacromolecules, exhibit remarkable dual functionality. They possess diverse pharmacological properties, including immunomodulation, anti-tumour activity and anti-inflammatory responses. Furthermore, polysaccharides have superior excipient properties. For instance, they enhance biocompatibility, ensure controlled biodegradability, possess efficient drug-loading capacity and exert stabilisation effects. With recent advancements in nanotechnology, polysaccharide based nanopharmaceutics and nano-delivery carriers have emerged as key areas of research. This review provides a comprehensive analysis of the pharmacological effects and excipient features of various polysaccharides and systematically expounds on their applications in nanocarriers. The findings are expected to advance the use of polysaccharides within the framework of drug–excipient unification theory. Ultimately, this review provides a theoretical basis and serves as a practical reference for modern pharmaceutics to achieve safer and more personalised treatment regimens.

Introduction

Polysaccharides are one of the four fundamental biomolecule types essential for life and occur widely in higher plants, crustaceans and algae. Polysaccharides exhibit various biological activities, including anti-tumour, anti-inflammatory, anti-bacterial, hypoglycaemic and immune-regulating effects (Lai et al., 2017), making them significant materials in multiple fields. In the medical domain, the bioactivity of polysaccharides has demonstrated considerable potential in disease treatment. For example, Ganoderma lucidum polysaccharides may benefit patients with cancer undergoing conventional chemotherapy or radiotherapy by boosting their immune function and mitigating the toxic effects of these treatments (Sohretoglu and Huang, 2018). Similarly, two novel polysaccharides isolated from Astragalus, APS-A1 and APS-B1, have demonstrated in vitro anti-inflammatory activity, indicating their potential as anti-inflammatory supplements (Chen et al., 2023). Chitosan has been used as an anti-microbial agent against bacteria, algae, yeast and fungi (Ruan et al., 2023). Furthermore, Polygonatum sibiricum polysaccharides can reduce insulin resistance index and lower blood glucose levels in diabetic mice (Wang et al., 2024). With the rapid advancement of nanotechnology, studies on the applications of polysaccharides as excipients have increased, particularly on their role as nanocarriers, which are significant in drug delivery and nanomedicine.

Drug–excipient unification refers to the replacement or reduction of traditional excipients with pharmacologically active ingredients that exhibit both therapeutic and excipient functions in a pharmaceutical preparation. In traditional formulations, the drug is the active ingredient that exerts therapeutic properties, whereas excipients (e.g., solvents, binders and disintegrators) are only used to improve the physical properties, stability or route of administration of the drug and thus do not have inherent therapeutic properties. Within the drug–excipient unification framework, excipients serve a dual purpose: they function as carriers for the formulation and are specifically designed to act synergistically with the primary drug. The excipient can enhance the therapeutic effects of the primary drug by enabling controlled release, facilitating targeted distribution or exhibiting inherent pharmacological activity. This concept differs from the traditional drug–excipient dichotomy and emphasises the dual role of functional ingredients in the carrier system. The mechanism of action includes synergistic interactions, delivery system optimisation (e.g. targeted delivery or controlled release), bioavailability enhancement, safety optimisation and toxicity reduction. Based on this concept, the use of components with pharmacodynamic effects as excipients can reduce the quantity and variety of other excipients in the formulation, thereby simplifying the prescription, reducing costs and enhancing safety. Notably, polysaccharides exemplify the characteristic of drug–excipient unification: they exhibit various physiological activities and can be directly used in disease treatment. Furthermore, polysaccharides function as excipients in formulations by providing a structure, functioning as a carrier and enhancing stability. Their functions include solubilisation, co-solvency, sustained release and controlled release. Overall, these properties enable polysaccharides to enhance clinical efficacy while minimising the required dosage, thereby reducing toxic adverse effects and alleviating gastrointestinal burden in patients. Therefore, polysaccharides exhibit significant potential for formulation-related applications.

This review provides a comprehensive overview of studies on the applications of polysaccharides in disease treatment and as excipients. The review also presents an in-depth discussion of the theoretical foundations and practical applications that illustrate the drug–excipient unification properties of polysaccharides based on studies retrieved through systematic searches conducted on PubMed, Google Scholar and ScienceDirect. These data sources ensure the scientific rigour and reliability of the analysis of the biological activities, physicochemical properties and application potential of polysaccharides, providing a solid foundation for further investigations into their diverse benefits in modern pharmaceutics.

The dual role of polysaccharides in medicine and as excipients is well-supported by baseline data in the literature. Based on these data, this review examines the guiding principles underlying the concept of drug–excipient unification. Furthermore, it systematically analyses the pharmacological activities and excipient characteristics exhibited by polysaccharides derived from various sources, including plants, marine fauna and algae. By analysing the potential uses of polysaccharides in drug delivery systems and novel formulation development, this review demonstrates how polysaccharides synergistically provide therapeutic and auxiliary benefits. Consequently, this review offers theoretical support and practical directions for overcoming bottlenecks in traditional formulation technologies and developing highly effective and safe novel drug delivery systems. These advancements promote the innovative use of polysaccharides in personalised precision medicine.

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Huan Yang, TianBao Zhang, Xuan Ma, FengYu Wang, Rui Yu, JunZi Wu, Multifunctional investigation of “drug–excipient unification” of natural polysaccharide nanocarriers: A new paradigm from drug delivery to adjuvant therapy, Carbohydrate Polymer Technologies and Applications, 2025, 100949, ISSN 2666-8939, https://doi.org/10.1016/j.carpta.2025.100949.