The electrostatic complexation of the protein beta-lactoglobulin (β-LG) with the anionic polysaccharide chondroitin sulfate (CS) and the subsequent stabilization by thermal treatment were studied to achieve the well-defined nanoparticles (NPs). The formation of the well-defined NPs was obtained at pH 4 with a hydrodynamic radius from 60 to 80 nm. NP aggregation was observed at pH 1.5 because of the loss of the anionic charge of chondroitin sulfate on the surface of the NPs. After thermal treatment, the NPs exhibited stability against a pH increase to pH 7 while a stronger aggregation at pH 1.5 was observed. Core-shell structures were found at pH 7 after thermal treatment, indicating a possible mechanism of partial disintegration. The addition of Tween 80 (T80) before thermal treatment led to the formation of T80 self-assemblies inside the NPs. This caused an increase in the hydrophobicity of the inner and outer surfaces of the NPs as it was observed by fluorescence spectroscopy. The ζ-potential of the complexes and NPs was about −20 mV while the presence of T80 did not affect it. FTIR spectra verified changes of the secondary structure of β-LG in its complexes with CS and T80. The thermally treated NPs exhibited high surface and overall hydrophobicity and stability in high salinity and biocompatible solutions. The thermally treated NPs showed colloidal and physicochemical stability for 1 month, which were enhanced by the addition of T80. Due to the nature of the precursors and their colloidal properties, the NPs are highly promising for applications as biocompatible drug delivery nanocarriers while T80 acts as an agent to modify their properties.

Among the most structurally diverse biomacromolecules, polysaccharides have attracted increased attention as nanocarriers for precision medicine due to their inherent biocompatibility and versatility in functionalization. Molecular features, such as monomer composition, glycosidic linkages, charge density, and chemical modification, essentially determine the nanoscale assembly process of these biopolymers, as well as their biological compatibility. This review highlights the role of these properties in the assembly process of polysaccharide-based nanocarriers leading to a variety of self-assembled nanostructures, such as polyelectrolyte complexes, protein–polysaccharide complexes, amphiphilic micelles, vesicles, hybrid systems, and nanogels, which are extensively discussed throughout the review. This review also focuses on the structure–property–function relationships of nanocarriers as applied to the rapidly developing area of precision medicine, emphasizing the problems of sustainability and reproducibility. By combining the principles of molecular engineering, supramolecular assembly, and measurable properties, this work aims to present a unified view of the molecular engineering of polysaccharide-based nanocarriers for enhanced translation potential, as well as to outline a coherent framework for the rational development of next-generation polysaccharide-based nanocarriers with improved clinical relevance.

Xanthan gum (XG) and diethylaminoethyl dextran (DD) electrostatic nanocomplexes (NCs) are prepared at the native (NCs) and thermally denatured state of XG (den-NCs). Dynamic and static light scattering (DLS and SLS) and transmission electron microscopy (TEM) reveal well-defined, spherical NCs with mean hydrodynamic and gyroscopic radii of 100-200 nm at charge ratios (ratio of anionic XG to cationic DD monomers) between 0.4 and 5. Their size increases at CR > 1 possibly due to XG-XG double helix formation. Surface potential shifts from positive to negative between CR 1 and 1.25, suggesting stoichiometric neutralization. NCs remain stable for over one month without significant aggregation. Fluorescence measurements with pyrene and 8-Anilino-1-naphthalenesulfonate (ANS) indicate the presence of hydrophobic domains inside the NCs attributed to DD's ethyl groups, which renders them suitable for the encapsulation of hydrophobic compounds. High loading efficiency (∼48 %) and loading capacity (∼19 %) for β-carotene (β-C) is found for native NCs at CR 0.4 and 2.5, whereas den-NCs show significantly lower encapsulation. NCs interact with porcine gastric mucin (PGM) in PGM solutions as it is confirmed by NC-PGM aggregation. Mucoadhesion is also examined with mucus-mimicking PGM-immobilized alginate beads. Positively charged NCs exhibit enhanced mucoadhesion relative to negatively charged ones. Overall, XG/DD NCs display tunable properties promising for drug delivery applications with notable stability, encapsulation and mucoadhesive capabilities.

Parenteral nutrition is an integral part of the nutritional support of critically ill neonates, infants, and children in the intensive care units (ICUs) and at home. Therefore, the adequacy and the effectiveness of parenteral nutrition, PN, support are among the major concerns of doctors and pharmacists. The aim of this study is the physicochemical and stability evaluation of nanoemulsions, which are used for parenteral nutrition. These nanoemulsions are for intravenous (IV) administration of lipids, amino acids, glucose, electrolytes, trace elements as well as vitamins. Light scattering techniques are used for the identification of the hydrodynamic diameter (D_h), size polydispersity index (PDI), and the ζ-potential of the prepared nanoemulsions. Stability assessment is performed in different conditions, mimicking those of the hospital. The stability studies involve shelf-life measurement of these NEs over 10 days in two storage conditions (25 °C and 4 °C) using dynamic light scattering. According to the US Pharmacopeia, the droplet size should be under the upper limit of 500 nm (0.5 μm). Transmission electron microscopy (TEM) is used for the shape of the droplets of the nanoemulsion emulsion for parenteral nutrition for the first time. The results showed that the droplet size was around 300 nm, with a homogeneous population and negative ζ-potential. The morphology was vesicular and spherical, typical for NE droplet shape. The results from all the characterization techniques show that the formulations meet the high-quality standards of nanoemulsions for neonates, infants and children.