Polysaccharide-Based Drug and Vaccine Delivery Systems for Infectious Diseases: Design Principles, Applications, and Translational Challenges

Abstract

The global burden of infectious disease remains substantial, compounded by antimicrobial resistance and persistent gaps in vaccine stability, immunogenicity, and equitable distribution. Conventional antimicrobial and vaccine formulations are frequently limited by poor aqueous solubility, rapid systemic clearance, chemical instability, and weak mucosal immune activation. Naturally derived polysaccharides including chitosan, alginate, dextran, starch, cellulose, and hyaluronic acid offer a structurally diverse, readily modifiable biomaterial platform for such systems by virtue of their biocompatibility, biodegradability, and, in several cases, intrinsic immunomodulatory activity. This review synthesizes the current literature on polysaccharide-based drug delivery systems for infectious disease control, examining their natural and semi-synthetic sources, key functional attributes (biodegradability, biocompatibility, and mucoadhesion), and the chemical modification strategies that fine-tune these properties for site-specific delivery. We evaluate the translational evidence for polysaccharide-based antimicrobial carriers, including chitosan–antibiotic nanoparticles, alginate wound-healing hydrogels, and dextran–antiviral conjugates, and for polysaccharide-based vaccine platforms that act as antigen-protective matrices and intrinsic adjuvants across oral, nasal, and parenteral routes; marketed polysaccharide-conjugate vaccines against S. pneumoniae, H. influenzae type b, N. meningitidis, and S. Typhi are discussed as clinical proof of concept. Finally, we critically appraise the translational barriers that constrain broader adoption—raw-material heterogeneity, batch-to-batch reproducibility, sterilization- and endotoxin-related quality concerns, and regulatory ambiguity around hybrid nanostructured carriers and outline the strategic directions, including stimuli-responsive carriers and integration with mRNA and recombinant-antigen technologies, required to accelerate clinical translation.