The success of a nano-scaled drug delivery system (DDS) depends on several factors, the most crucial of which is enhancing the drug's overall activity. This includes increasing its bioavailability by safeguarding the drug from enzyme degradation, avoiding non-specific targeting in the body, prolonging its half-life in the bloodstream, overcoming blood-organ barriers, and enhancing its retention in the target tissue. As a result, the drug's half-maximal inhibitory concentration (IC50) value is reduced. The carrier's biocompatibility and biodegradability ensure no chance of cytotoxicity [1].

Polysaccharides (PS) are long chains of mono- or oligosaccharides, sourced from plants, animals, and microbes, offering a biodegradable carrier matrix [2]. The classification of PSs is contingent upon the attributes of their repeat units, namely their identity and the type of glycosidic bonds. The common repeat units found in PSs are glucose and its derivatives, such as fructose and galactose. Homopolysaccharides (e.g. cellulose, starch, glycogen, and dextran) and heteropolysaccharides (e.g. alginate (ALG), chitosan (CS), and hyaluronic acid (HA) possess identical and distinct repeat units, respectively. The origin of PSs determines their grouping as plant- (starch, cellulose), algae- (ALG, and carrageenan), animal- (glycogen, chitin, and glycosaminoglycans), or microorganism-derived (dextran, xanthan, and pullulan) biopolymers. Naturally sourced PSs can either be charged or neutral and soluble or insoluble in water. For instance, CS carries a positive charge due to the partial protonation of its primary amine groups under physiological conditions (pH = 7.4). Negatively charged PS (contains sulfate or carboxylate groups) on the other hand, have a low pKa value and are deprotonated at a neutral pH [3]. Fig. 1. Nano-scaling such biomaterials can intensify their efficacy in the biological milieu, and drug carriers derived from them are anticipated to possess the attributes of both a bioactive agent and a directing ligand [4], resulting in an amplified therapeutic effect. An example is the synergistic enhancement of lysozyme's antibacterial effect (by 2-fold) when combined with Ulvan poly-electrolyte complex (PEC). This is attributed to the enhanced penetration of nanoparticles and an improved charge-to-volume ratio [5].

They solely or in combination with other classes of nanocarriers provide advantages in biomedical applications that are absent in formulations lacking them as described in Table 1. The nanoparticulate carriers derived from PSs possess exceptional properties. PS displays excellent mucoadhesion, allows an evasion from the reticuloendothelial system (RES) [6], and possesses anti-inflammatory attributes and they can be chemically modified to introduce properties such as tumor cell internalization [7], and thermoresponsive [8]. Polysaccharides such as Hyaluronic Acid (HA) and Chondroitin Sulfate exhibit intrinsic receptor targeting capabilities, specifically targeting CD44 overexpressing tumor cells [9]. Ulvan demonstrates a notable affinity for P-Selectin receptors [10], while Angelica sinensis PS and Pullulan exhibit promising potential for liver targeting [11]. Moreover, Gracilaria lemaneiformis PS has exhibited affinity for αvβ3 integrin, which is overexpressed in glioma cells [12]. Their NPs have good surface properties, such as a large surface area, good drug loading capacity, binding ability towards ligands and small molecules, surface charge, and hydrophilicity. These properties make them stable, targetable, and able to modulate a drug’s biodistribution, Thus, PSs possess desirable structural properties that make them an excellent starting material for designing nano-DDSs.

Enhanced drug delivery is the efficient parcel of drugs from the site of administration to the site of action, ensuring that the drug effectively reaches its target. It can be achieved by a combined force of optimized carrier matrix material and carrier design. Thus, to design an effective delivery system, the key is to choose the matrix material based on the targeted location, followed by selecting the drug and identifying its interaction with the carrier. Intelligent ideas are then applied to make use of the backbone material's functional versatility, along with a vast library of synthetic procedures, to design DDSs that are multi-responsive and multi-functioning. There are a variety of PS-derived nanostructures. Some of the most important that form the basis of successful drug delivery systems, like nanogels (NGs), nano-micelles, and polymersomes, will be discussed in this review. This review aims to analyze important factors for enhancing drug delivery aspects using polysaccharide-based nanoparticles.