**Background:** Polysaccharides are natural macromolecules with diverse biological activities (e.g., antitumor, immunomodulatory, antioxidant) and are widely used in biomedical applications. Their biocompatibility, biodegradability, and ability to form hydrogels, nanoparticles, and nanofibers make them attractive for controlled drug delivery. This review focuses on the principles, kinetics, and modeling of drug release from nanoengineered polysaccharide systems, including nanofibers and nanoparticles.
**Methods:** The paper is a narrative review that synthesizes existing literature on polysaccharide-based drug delivery systems. It discusses the chemistry of polysaccharides (e.g., cellulose, chitosan, alginate, pectin, hyaluronic acid), their classification by source (plant, animal, microbial, algal), and their modification for drug encapsulation. The review covers drug release mechanisms (diffusion, swelling, erosion) and mathematical models (zero-order, first-order, Higuchi, Korsmeyer-Peppas, Weibull, etc.) used to describe release kinetics. It also summarizes studies on drug-loaded polysaccharide systems, including antibiotics, anticancer drugs, and natural extracts, with specific examples of release profiles and model fitting.
**Key Results:** The review presents numerous examples of drug release from polysaccharide matrices. For instance, tetracycline hydrochloride (TCH)-loaded poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin/chitosan nanofibers showed 96.5% total drug release with 11.8% initial burst, and release followed the Korsmeyer-Peppas model (R² ~0.98–0.99) with n values <0.5, indicating pseudo-Fickian diffusion. Curcumin-loaded chitosan/pectin nanofibers exhibited pH-responsive release, with the highest R² (0.9485) for first-order kinetics at pH 5.4. Starch-quercetin nanoparticles were best described by the Peppas-Sahlin model (R² >0.99), with Fickian diffusion dominating (k₁ >> k₂). Capsaicin-loaded indica rice starch nanoparticles showed first-order and Korsmeyer-Peppas models as best fits (R² >0.9), with n values <0.45 indicating Fickian diffusion. Pectin nanoparticles for S-adenosyl-l-methionine delivery had Korsmeyer-Peppas as the best model (R² = 0.9969, n = 0.376). The review also notes that drug release can be tuned by factors like polymer composition, crosslinking, pH, and drug loading.
**Clinical Implications:** Polysaccharide-based nanoengineered systems offer significant advantages for controlled drug release, including improved bioavailability, reduced dosing frequency, and targeted delivery. Their mucoadhesive properties and ability to respond to physiological stimuli (pH, enzymes) make them suitable for oral, ocular, transdermal, and colon-specific delivery. The review emphasizes the importance of mathematical modeling to predict release kinetics and optimize formulations. However, it notes that most research is at the academic level, and translation to clinical trials requires addressing manufacturing scalability, regulatory approval, and in vivo validation. Future trends include personalized medicine, theranostics, and cell-based therapies using polysaccharide matrices.