Fucoidan in Pharmaceutical Formulations: A Comprehensive Review for Smart Drug Delivery Systems

Fucoidan encompasses a heterogenous class of polysaccharides found in the extracellular matrix and cell wall of brown seaweeds (Phaeophyta) and marine invertebrates with potential physiological functions. It acts as cellulose and hemicellulose cross-linkers, playing a crucial role in cell wall integrity, in addition to preventing algae dryness during summer and low tide periods, among others [1,2]. Chemically, fucoidan is composed of a sulfated backbone of diverse sugar monomers, mainly L-fucose, as well as galactose, glucose, xylose, mannose, and uronic acids. However, some proteins and minerals such as calcium, magnesium, manganese, copper, potassium, selenium, sodium, and zinc can be also found [3]. The heterogeneity in fucoidan’s chemical composition regarding monomeric composition, glycosidic linkages, sulfation pattern and content, presence of other constituents, and molecular weight has been investigated extensively in the past few years.

These variations are mostly associated with different factors, including algae species, season of harvesting, extraction processes, geographical origin, and vegetative phase [4,5,6,7]. The diversity in fucoidan’s biochemical composition has enriched various scientific fields with investigations of potential bioactivities and applications. For instance, fucoidan either with low, intermediate, or high molecular weight has gained much interest recently due to its promising biological and pharmacological properties such as heparin-like anticoagulant, antitumor, anti-angiogenic, anti-inflammatory, anti-hyperglycemic, antiviral, and immunomodulatory bioactivities [8,9,10,11]. As a result, fucoidan-containing products are consumed widely for nutraceutical and health-promoting benefits based on unique molecular mechanisms. Liu et al. reported that fucoidan can be beneficial as a nutraceutical product against obesity and abnormal lipid accumulation within cells through regulating cellular glucose consumption as it reduces glycerol-3-phosphate dehydrogenase (GPDH) functionality. Furthermore, high-molecular-weight fucoidan extracted from Fucus vesiculosus has also been found to have antioxidant, antihyperglycemic, anti-inflammatory, and anticoagulant effects which are attributed to multiple mechanisms, including the inhibition of dipeptidyl peptidase-IV enzyme as one of the possible mechanisms involved in the anti-hyperglycemic activity of fucoidan, and its selective inhibition of the cyclooxygenase-2 (COX-2) enzyme, responsible for its anti-inflammatory effect [12]. Other reported mechanisms include the role of fucoidan in modulating oxidative stress and gut microbiota [13,14].

Further investigations have confirmed this activity in perfluorooctanoic acid-associated obesity in an animal model [15]. These fucoidan products used the dried fucoidan extract derived from Undaria pinnatifida (a type of brown seaweed) for the preparation of functional foods in the form of cookies and noodles [16]. Edible films are another formulation technique for incorporating fucoidan into alginate-chitosan gel films as nutraceuticals with antioxidant and anti-inflammatory effects [17]. Other cosmeceutical applications (e.g., anti-photoaging and skin protective activity) were shown for fucoidan products against UVB irradiation via its antioxidant effect and its inhibition of oxidative stress markers and matrix metallopeptidase-9 (MMP-9) expressions [18].

Fucoidan also offers some attractive physical properties enabling its use in diverse pharmaceutical formulation techniques (Figure 1). These physical characteristics include, for instance, mucoadhesion, pH, temperature, and enzyme response. In addition, fucoidan has a strong ability to bind to numerous compounds and macromolecules. The binding affinity is mainly resulting from the negatively charged surface, the degree of sulfation, and molecular weight. Additionally, fucoidan has low apparent viscosity with a pseudoplastic flow, preventing its use as a gelling or thickening agent. On the other hand, upon mixing fucoidan with oppositely charged polymers, gel, matrices, and films can be formed. Moreover, fucoidan is known for its high stability under acidic and alkaline conditions [19].