Bioactivities and Pharmaceutical Applications of Algal Phycocolloids

Bioactivities and Pharmaceutical Applications of Algal Phycocolloids: Comparison

Please note this is a comparison between Version 1 by Ana Marta Gonçalves and Version 2 by Lindsay Dong.

Seaweeds are abundant sources of diverse bioactive compounds with various properties and mechanisms of action. These compounds offer protective effects, high nutritional value, and numerous health benefits. Seaweeds are versatile natural sources of metabolites applicable in the production of healthy food, pharmaceuticals, cosmetics, and fertilizers. Their biological compounds make them promising sources for biotechnological applications. In nature, hydrocolloids are substances which form a gel in the presence of water. They are employed as gelling agents in food, coatings and dressings in pharmaceuticals, stabilizers in biotechnology, and ingredients in cosmetics. Seaweed hydrocolloids are identified in carrageenan, alginate, and agar. Carrageenan has gained significant attention in pharmaceutical formulations and exhibits diverse pharmaceutical properties. Incorporating carrageenan and natural polymers such as chitosan, starch, cellulose, chitin, and alginate. It holds promise for creating biodegradable materials with biomedical applications. Alginate, a natural polysaccharide, is highly valued for wound dressings due to its unique characteristics, including low toxicity, biodegradability, hydrogel formation, prevention of bacterial infections, and maintenance of a moist environment. Agar is widely used in the biomedical field.

seaweed
polysaccharides
carrageenan
alginate
agar

1. Introduction

The demand for healthy and natural products from health-conscious consumers has led to significant growth in the global hydrocolloids market. Hydrocolloids find applications in various industries such as oil, food, paper, paint, textiles, and pharmaceuticals. Their diverse range of functions plays a crucial role in driving the market forward. The primary types of hydrocolloids include gelatin, pectin, xanthan gum, and guar gum.

Among these, gelatin holds the largest share in the food hydrocolloids market due to its extensive use as a gelling agent in confectionary, meat, poultry, and dairy products. Hydrocolloids can be classified as natural, semisynthetic, or synthetic, depending on their origin. Natural hydrocolloids are hydrophilic biopolymers derived from plants, animals, or microbes. Plant-derived hydrocolloids are primarily used to stabilize oil-in-water emulsions, while animal-derived hydrocolloids tend to form water-in-oil emulsions.

However, animal-derived hydrocolloids can potentially cause allergies and are prone to microbial growth and rancidity. Semisynthetic hydrocolloids are synthesized by modifying naturally occurring hydrocolloids. Examples of semisynthetic hydrocolloids include starch and cellulose derivatives such as methylcellulose (MC), carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), acetylated starch (AS), phosphorylated starch (PS), and hydroxypropylated starch (HPS). These semisynthetic hydrocolloids exhibit stronger emulsifying properties, are nontoxic, and are less prone to microbial growth. On the other hand, synthetic hydrocolloids are completely synthesized in industries using petroleum-derived base materials. They are the most potent emulsifiers and do not support microbial growth, but their costs can be prohibitive. Synthetic hydrocolloids are primarily used as oil-in-water emulsifiers. However, semisynthetic hydrocolloids are generally preferred over purely synthetic gums ^[1][2][1,2].

Various hydrocolloids, including guar gum, carrageenan, xanthan gum, gum arabic, pectin, and others, have demonstrated potential in preserving and safeguarding pharmaceutical drugs from external stresses [3]. Guar gum possesses inherent gelling properties, pH-responsive behaviour due to its ionic groups, and vulnerability to bacterial and enzyme degradation in the large intestine. These characteristics make it an excellent choice as a carrier for drug delivery targeted specifically to the colon [4]. This water-soluble polysaccharide has been utilized in various forms such as matrix tablets, compression-coated tablets, nanoparticles, and hydrogels. Additionally, significant research highlights the application of guar gum in protein delivery, antihypertensive medications, and transdermal drug delivery systems ^[4][5][4,5]. However, a notable limitation of its usage stems from its high swelling properties, which can result in the rapid release of loaded drug molecules [6]. Hydrocolloids can be derived from both renewable and non-renewable resources. However, there is a growing preference for renewable hydrocolloids due to economic and ecological considerations. In response to the increasing consumer demand for all-natural products, the goal is to replace nonrenewable and synthetic hydrocolloids with renewable alternatives in various industrial applications. This drives the search for novel natural hydrocolloids that can offer unique features for specific purposes [7].

In the food and pharmaceutical industries, natural hydrocolloids are highly favoured over semisynthetic and synthetic hydrocolloids. This preference is due to their numerous distinct advantages, which contribute to enhancing the stability, functionality, quality, safety, and nutritional value of various products. Natural hydrocolloids possess several notable benefits compared to their counterparts, including being extracted from renewable sources, readily available and easy to work with, biocompatible, nontoxic, capable of physical and chemical modification, environmentally friendly, cost-effective, and widely accepted by the public due to the multitude of health benefits they offer [8].

Therefore, there is a growing interest in seaweeds as sources of hydrocolloids. The historical utilization of seaweeds, also referred to as macroalgae, for medicinal applications can be traced back to Asian countries. These cultures explored the remarkable benefits of seaweeds and incorporated them as alternative healing methods. Seaweeds are categorized into three groups: brown algae (Ochrophyta, class Phaeophyceae), red algae (Rhodophyta), and green algae (Chlorophyta). Every division contains an assortment of bioactive substances displaying diverse properties and mechanisms of action. In addition to their protective actions, seaweed metabolites offer a high nutritional content and numerous health advantages ^[9][10][9,10]. Seaweeds have proven to serve as versatile natural stores of different metabolites [11]. Multiple research studies showcase that bioactive compounds derived from seaweeds have applications across various sectors, including the production of wholesome edibles [12], pharmaceutical formulations [13], and cosmetic commodities [14]. Algal compounds are harnessed for the manufacturing of food products, animal feed, beauty items, and fertilizers ^{[15][16][17][18][19]}[15,16,17,18,19].

Hydrocolloids derived from seaweeds, such as agar, carrageenan (abundant in Rhodophyta), and alginates (abundant in Phaeophyceae), are extensively harvested and employed across multiple sectors. They serve as gelling agents in food and dressings, coatings in pharmaceutical products, stabilizers in biotechnology, and ingredients in cosmetics such as moisturizers, body lotions, hair cleansers, and dental paste ^[20][21][24,25]. By exploring their beneficial qualities, there is potential for the creation of targeted functional food products tailored to different needs and suitable for medical purposes ^[22][26]. Carrageenan has gained significant interest and its usage in pharmaceutical formulations has increased. It has been incorporated into recognized pharmacopoeias such as the United States Pharmacopeia 35-National Formulary 30 S1 (USP35-NF30 S1), British Pharmacopoeia 2012 (BP2012), and European Pharmacopoeia 7.0 (EP7.0), indicating its potential as a pharmaceutical excipient and a promising future ^[23][27]. Carrageenan has demonstrated various pharmaceutical properties such as antiviral and antimicrobial properties ^{[24][25][26][27][28]}[28,29,30,31,32], but also anticoagulant effects ^[29][30][33,34], antidiabetic ^[31][32][35,36] and antioxidant activity ^[33][34][35][37,38,39], and more. There is a growing interest in utilizing mixtures and combinations of carrageenan with natural polymers such as chitosan, starch, cellulose, chitin, and alginate, which are explored to create biodegradable materials with favourable characteristics for use in biomedical applications. These combinations have shown significant potential in various biomedical purposes, including drug delivery and tissue engineering ^[36][40]. Alginate, a polysaccharide found in nature, is highly valued for its applications in manufacturing wound dressings due to its unique characteristics. These include low toxicity, biodegradability, cost-effectiveness, the ability to form hydrogels, prevention of bacterial infections, and the ability to maintain a moist environment ^[37][38][41,42]. Agar or agar-agar, a unique naturally occurring polymer, is increasingly preferred over synthetic polymers and is being explored as an alternative raw material for medicinal applications. It holds significant appeal in the pharmaceutical sector due to its exceptional inherent qualities, particularly the strong gel it forms. Agar-agar has been utilized in the development of injectable and phase-changeable composite hydrogels for treating cancers with chemo and photothermal therapy. These composite hydrogels can effectively load and release chemotherapeutics and antibiotics. Additionally, an agar-based nanocomposite film has demonstrated effectiveness in inhibiting the growth of Listeria monocytogenes ^[39][43]. In the pharmaceutical industry, the use of agar and polysaccharide blends is also gaining popularity. Agar-agar primarily serves as a gelation, stabilization, and thickening agent in pharmaceuticals. Moreover, it is commonly employed for purgative purposes and as a surgical aid. Researchers have dedicated efforts to creating agar-based products such as composite hydrogels, nanocomposite films, and other materials specifically to be applied in the field of pharmacology ^[39][43]. The combination of agar molecules with the lowest concentrations of charge results in the formation of agarose exhibits excellent gel-forming ability. Agar, on the other hand, is present in varying amounts with complexed molecules and different levels of charged groups. The capacity of agar to withstand hydrolysis is crucial for its application in bacteriology. When preparing culture media, agar’s strong gel-strengthening property and lack of cations with hysteresis contribute to the production of high-quality solid microbial cultures. Agarose finds a wide range of uses in biotechnology, and the increasing number of innovative applications is expected to drive the demand for high-quality agarose in the field ^[40][44]. Agar derivatives have also found applications in dentistry and biotechnology, such as dental prosthesis, material shaping, and plant culture tissues ^[41][45].

2. Seaweeds Phycocolloids

2.1. Carrageenan

Red algae contain a type of polysaccharides called carrageenans ^[42][46]. These carrageenans consist of galactans, which can form a gel in aqueous or milk solutions. These compounds are extensively employed in the food, cosmetic, and pharmaceutical sectors. As a result, extracts from red algae containing carrageenans are commercially utilized ^[43][44][47,48]. Carrageenan, illustrated in Figure 1, is a linear polysaccharide composed of sulphated or nonsulphated galactose units linked together through α-1,3-glycosidic and β-1,4-galactose bonds ^[45][49]. These natural polysaccharides consist of a mixture of sulphated linear galactans. The structural units are composed of disaccharides, specifically α-(1→4)-linked d-galactopyranose (D) residue or 3,6-anhydrogalactopyranose (DA), and β-(1→3)-linked d-galactopyranose (G) residue. The sulphate groups are bound by covalent bonds to the galactose atoms C-2, C-4, or C-6 through ether bonds ^[42][46].

Figure 1.

Chemical structure of κ-carrageenan.

Carrageenans can be classified into various types (κ-carrageenan, ι-carrageenan, λ-carrageenan, γ-carrageenan, ν-carrageenan, ξ-carrageenan, θ-carrageenan, and µ-carrageenan) based on the position of the sulphate group attached to the galactose unit. In nature, carrageenans are predominantly hybrid, leading to variations in their properties depending on the specific bonded sulphate group ^[46][50]. These carrageenans are typically categorized into three structural configurations (κ-, ɩ-, and ʎ-) according to the quantity of sulphated groups attached to the galactose unit; the presence, chemical position, and organization of these groups govern the function and bioactive properties of carrageenan ^[47][51].

Different species yield distinct types of carrageenans. κ-carrageenans, readily accessible in the market, are extracted from Kappaphycus alvarezii through a heat extraction method. In contrast, λ-carrageenans are typically derived from red algae species found in the Gigartina or Chondrus genera through drum drying or ethanol precipitation methods ^[48][52]. These carrageenans are found in various families such as Solieriaceae, Rhabdoniaceae, Phyllophoraceae, Gigartinaceae, Rhodophilidaceae, and Thichocarpaceae. Among these, eight carrageenan sources are exclusive to the Japanese Sea (East Sea), with Chondrus pinnulatus, Chondrus armatus, Chondrus yendoi, Mastocarpus pacificus, and Mazzaella hemisphaerica belonging to the Gigartinaceae and Solieriaceae families.

In contrast, ɩ-carrageenan is primarily derived from Eucheuma denticulatum (commonly known as “spinosum”), and it imparts a soft and weak gel consistency. Lastly, ʎ-carrageenan is obtained from various species of the Gigartina and Chondrus genera ^[49][53].

Carrageenans find extensive use in the food industry due to their ability to gel, thicken, and stabilize food products ^[50][54]. The commercial forms of ʎ-, κ-, and ɩ-carrageenans have been approved as food additives by regulatory bodies such as the Food and Drug Administration (FDA) and the European Food Safety Agency (EFSA) ^[51][55].

Water solubility is characteristic of all carrageenan variants, albeit their solubility in aqueous solutions is subject to influence from factors such as temperature, pH, ionic strength, and the presence of cations. The hydrophilic nature of carrageenans stems from the sulphate and hydroxyl groups, while their hydrophobic characteristics mainly arise from the 3,6-anhydro-α-D-galactopyranose units ^[50][54]. The hydrophobicity of carrageenan presents a drawback in the production of water-resistant packaging. However, one potential solution to enhance the properties of carrageenan is to combine it with hydrophobic compounds to reinforce the material’s matrix. This approach could result in ecofriendly and cost-effective packaging materials with improved strength, as well as potential therapeutic applications ^[52][59].

2.2. Agar

Agar has a chemical structure distinguished by recurring units of D-galactose and 3,6-anhydro-L-galactose, with minor deviations and a low level of sulfate esters (Figure 2); carrageenan comprises two groups of polysaccharides: agarose, an uncharged polysaccharide, and agaropectin, a simplified term for the charged polysaccharide ^[53][54][55][62,63,64]. Agarose is responsible for agar’s ability to form gels, making it a valuable ingredient in skincare, herbal medicine, and pharmaceuticals. Additionally, it has exceptional film properties ^[56][65].

Figure 2.

Chemical structure of agarose polymer.

Agar is a term utilized to describe a blend of gelling polysaccharides composed of d-galactose and l-galactose ^[57][66]. This combination is synthesized within the cellular wall matrix of red seaweeds and maintains a gel-like structure at room temperature ^[58][67]. The specific polysaccharide, known as agarose (Figure 2), is characterized by repeating units of d-galactose and 3,6-anhydro-l-galactose linked together by β-1,3- and α-1,4-glycosidic bonds. Agarose makes up to 70% of the total polysaccharide content in agar ^[59][68].

Due to their functions as stabilizers, emulsifiers, and thickeners, agar is widely utilized in the commercial food processing sector. These additives are commonly found in gel-based food products such as desserts, preserves, jellies and baked goods. Agar in gel form typically exhibits a firm and transparent texture, but its strength can be enhanced by incorporating sugars ^[60][69]. One advantage of agar is its low hygroscopic property, which is beneficial for packaging production. Additionally, agar films are biologically nonreactive and exhibit a propensity to interact with different bioactive compounds and/or plasticizers, thereby facilitating the production of elastic and soft gel formations ^[61][62][63][70,71,72].

Agar and other polysaccharides play a crucial role in providing protection to algae against pathogens, maintaining cellular ionic balance, and safeguarding them from extreme conditions such as salinity, pH, temperature variations, and desiccation ^[64][65][73,74].

2.3. Alginate

The key polysaccharide in this context is alginic acid, also known as algin or alginate (Figure 3). These polysaccharides can be derived from the cell walls of brown algae, including species such as Macrocystis pyrifera, Laminaria hyperborea, Ascophyllum nodosum, as well as various bacterial strains ^[66][81]. Alginate, derived from alginic acid and its derivatives and salts ^[50][67][54,82], accounts for 10% to 40% of the dry weight of untreated algae and comprises 30–60% of the total sugars in brown seaweeds ^[68][83]. Alginates are anionic linear polysaccharides present in significant amounts in brown seaweeds, constituting up to 40% of the dry weight, and they have been acknowledged for their capacity to create edible films.

Figure 3.

Chemical structure of alginic acid.

These alginates are composed of polymers of alginic acid, with monomer units of β-D-mannuronic acid (M) and α-L-guluronic acid (G) joined by 1,4 linkages ^[69][70][84,85]. The physicochemical and mechanical properties of alginate gels differ based on the M/G ratio and the length of the structure. A higher content of guluronic acid contributes to stronger gelling characteristics and the formation of more elastic gels. On the other hand, lower M/G ratios yield sturdy and brittle gels that demonstrate excellent heat stability but may exhibit syneresis during the freeze–thaw cycle ^[50][67][54,82]. With its remarkable stabilizing and thickening abilities, alginate is extensively utilized in various food and medical applications ^[50][67][71][54,82,86]. Due to their high hydrophilicity, alginates require the incorporation of additional components within the matrix to enhance water resistance. Furthermore, the presence of ions impacts the solubility of alginates, and the formation of gels relies on the type of bonds formed with cations ^[50][67][54,82]. Introducing calcium into the alginate matrix enhances stability and resilience, offering potential for the creation of biodegradable materials with antimicrobial properties and nontoxic packaging ^[71][72][86,87]. Due to their high hydrophilicity, alginates require the incorporation of other components into the matrix to enhance their resistance when in contact with water. Furthermore, the solubility of alginates is influenced by the presence of ions, and the formation of gels depends on the specific bonds formed with cations ^[50][67][54,82].

3. Physical-Chemical Properties of Algal Phycocolloids

When evaluating the quality of an optimal material for the preparation of scaffolds or hydrogels, it is essential to consider mechanical properties such as tensile strength, elongation at break, heat resistance, and water vapour permeability. Tensile strength refers to the maximum stress a material can withstand before breaking when stretched or subjected to pressure. Generally, the tensile strength and Young’s modulus of plant fibres increase with higher cellulose content. Elongation at break is the ratio between the modified length and the initial length of the tested material after it fractures. It indicates the material’s ability to undergo shape changes without developing cracks in a matrix composed of natural polymers. Thermal resistance is a thermal property that represents the temperature difference a material can withstand ^[73][105]. Vapour permeability, on the other hand, pertains to a material’s ability to allow the passage of vapours, such as water vapour or other gases. According to ISO 11092:1993 ^[74][106], water vapour permeability is a characteristic influenced by the water vapour resistance of a textile material or composite. A higher permeability value indicates that water and vapour can pass through the material more quickly, which is desirable. The gelling properties of phycocolloids extracted from seaweeds vary depending on factors such as their structure, concentration in a solution, temperature, pH, and syneresis potential ^[75][76][77][107,108,109]. The physicochemical attributes of phycocolloids are extensively influenced by factors such as species, environmental circumstances, extraction methodologies, and treatment procedures ^[75][78][107,110]. Therefore, it is crucial to possess a comprehensive understanding of these factors to discover the most effective techniques for obtaining high-quality phycocolloids with optimal mechanical properties. Carrageenans, in their salt form, exhibit significant gel strength ^[79][111]. Among them, κ-carrageenan and ι-carrageenan gels remain stable at room temperature, while λ-carrageenan, being the only carrageenan soluble in cold water in its natural state, does not gel. The addition of cations enhances gel formation and strength in κ-carrageenan phycocolloids, as reported by Robal et al. ^[80][112].

4. Therapeutic Applications of Phycocolloids

4.1. Carraagenan

Studies have provided evidence that carrageenans possess interesting biological activities ^{[81][82][83][84][85]}[57,58,143,144,145]. Polysaccharides characterized by the highest degree of sulfation and molecular weight, as well as the most notable in vitro antioxidant capacity, were obtained by sequentially extracting carrageenan from Mastocarpus stellatus using water, acid, and alkali ^[86][124]. Several studies have reported the enhanced activity of antioxidant enzymes, including catalase and superoxide, in the presence of carrageenans ^[87][146]. Carrageenan has been demonstrated to induce apoptosis in various cancer cell lines. In particular, the red alga Porphyra yezoensis has shown the ability to induce dose-dependent cancer cell death through apoptosis in in vitro tumour cell lines, while not exhibiting cytotoxicity against healthy cells ^[88][125]. In the same study, the ability of carrageenans derived from K. alvarezii to reduce the growth of liver, colon, breast, and osteosarcoma cell lines was detected. Additionally, several studies have reported the antiproliferative effects of carrageenans in in vitro cancer cell lines, as well as the inhibition of tumour growth in mice ^[89][90][126,127]. Carrageenans have also exhibited antimetastatic effects by impeding the interaction of cancer cells with the basement membrane, inhibiting tumour cell growth, restraining tumour cell growth, and preventing adhesion to different substrates. However, the exact mechanisms of action remain unidentified. In the beginning, λ-carrageenan obtained from the red algae Gelidium cartilagenium exhibited antiviral properties against the influenza B virus or mumps virus ^[91][130]. The antiviral activity of carrageenan is attributed to its capacity to shield specific cellular structures involved in virus–receptor interaction ^[92][151]. The antiviral effect of λ-carrageenan can be attributed to the formation of enduring virion–carrageenan complexes that are irreversible, thus occupying the viral envelope sites necessary for virus attachment to host cells and hindering the virus from completing the infectious cycle ^[93][94][152,153].

4.2. Alginate

Alginate hydrogels have also gained recognition for their various benefits in wound healing, including reduced scarring, minimal bacterial infection, promotion of cell proliferation, enhancement of cytokine activity, regulation of pain and inflammation, and creation of a moist wound environment ^[38][95][42,155]. These hydrogels have also shown promise in tissue regeneration and drug delivery, as they possess a structural resemblance to the extracellular matrix, allowing them to perform critical functions in wound management ^[96][156]. Dry films composed of alginate-based dressings are well suited for the treatment of superficial wounds that exude fluid. When an alginate-based dressing is applied to a wound with a moderate to high level of exudate, the alginate component within the dressing absorbs the fluid, effectively preventing maceration of the surrounding tissues and promoting wound healing ^[37][41]. Alginate, a biomaterial that forms a gel upon the introduction of divalent calcium ions (Ca²⁺), has been extensively investigated and employed in diverse domains such as wound healing, tissue engineering ^[97][159], orthopaedics, and dental implant surgery. Its key benefits include low toxicity, cost-effectiveness, biocompatibility, and osteoconductive ^[98][99][160,161]. Alginate hydrogels are utilized in the field of wound healing for the development of wound dressings ^{[100][101][102][103]}[162,163,164,165]. Numerous studies have demonstrated that drugs encapsulated within alginate hydrogels exhibit improved bioavailability compared to the free form of the drug directly applied to the wound site, leading to enhanced healing efficacy. Moreover, alginate hydrogels find extensive applications in tissue regeneration and cell encapsulation therapies ^{[104][105][106][107][108][109][110]}[166,167,168,169,170,171,172]. Alginate is commonly employed in the fabrication of capsules for cell encapsulation, which is often associated with cytotherapy treatments or the creation of cellular microcultures within more complex systems. Alginate-derived hydrogels currently offer several advantages, making them suitable materials for applications in tissue engineering and regenerative medicine ^{[111][112][113]}[173,174,175]. The ionotropic alginate hydrogel biomaterial has gained significant attention in the fields of tissue engineering and regenerative medicine due to its biocompatibility, non-thrombogenic nature, mild gelation process, and similarity to the extracellular matrix (ECM). As a result, it has been widely utilized as a drug delivery system in these domains ^[114][176].

4.3. Agar

Agar is a colloidal substance extracted from various red algae species that has gained widespread use in several sectors regarding biomedicine, chemicals, and the alimentary services, primarily as a gel-forming agent, thickener, water-holding agent, and stabilizer. The properties of agar, including its affordability, thermoreversibility, and high-strength nature, contribute to its increasing utilization across various industries. The chemical composition of agar, such as its sulphate, methoxyl, and sugar contents, influences its application in different products, and this composition can be affected by various extraction process variables. With its remarkable gelling power and the ease of extraction, agar holds promise as an environmentally friendly material due to its renewability and biodegradability. While previous research has focused on utilizing agar or alginate alone for oral drug delivery, there is limited exploration of blending agar with natural or synthetic polymers to modify its properties ^[115][185]. Agarose solutions exhibit the ability to form reversible gels upon cooling below 40 °C through physical cross-linking ^[65][74]. This property, along with its unique mechanical characteristics and biocompatibility, has made agarose widely used in various applications such as cosmetics, biomedical applications, cell therapies, drug delivery, tissue engineering, and molecular biology. While native agarose hydrogels are generally not suitable for cell adhesion and growth due to their high hydrophilicity and antiadhesive properties, this feature is advantageous in hydrogel dressings. It prevents tissue ingrowth into the matrix, minimizing potential damage to the healing wound upon removal ^[116][140]. The inclusion of agar in the hydrogel led to notable improvements in mechanical properties, including increased compressive strength and shear stress, which can be attributed to the higher Young’s modulus of the added compound. Importantly, the addition of agar enabled injectability of the hydrogel through a syringe needle, overcoming a significant limitation of using GG as a biomedical device. The morphology of the materials exhibited an appropriate porous microstructure, with a porosity range of 70 to 180 µm, facilitating optimal water uptake for improved mechanical properties, as well as effective diffusion of nutrients, oxygen, and cell ingrowth.

5. Phycocolloids as Potential Drug Delivery System

The common employed practice for regulating the release of drugs is through the utilization of oral extended-release tablets consisting of a solitary hydrophilic matrix system. The properties of carrageenan, such as its elevated molecular weight, high viscosity, and gelling capabilities, make it a suitable choice for serving as the matrix in the creation of extended-release tablets. However, its capacity for loading drugs is limited. In order to surmount this constraint, the combination of polymers has been extensively employed over many years to effectively adjust drug release and achieve desirable outcomes ^[117][188].

The impact of polymer blends that include carrageenans (τ, ʎ) and cellulose ethers (HPMC, sodium carboxymethylcellulose, methylcellulose, hydroxypropyl cellulose) on the release of ibuprofen from tablets, produced through direct compression, was examined. Most of the formulations displayed consistent release patterns, and the release of ibuprofen was sustained for a duration of 12–16 h ^[118][189].

Carrageenan has demonstrated its ability to regulate early drug dumping, making it a promising option for achieving consistent drug release. A study revealed that incorporating as much as 40% ʎ-carrageenan in the matrix (ʎ-carrageenan-HPMC) effectively controlled the initial release of drugs, such as salbutamol sulphate and chlorpheniramine maleate, with release profiles closely resembling linearity ^[119][192]. The mechanisms responsible for the reduction in burst release were explained by the interaction between the basic drug and ʎ-carrageenan at the surface of the tablet, which hindered drug diffusion, while the main determinant of drug release was the erosion of the carriers ^[120][194]. The combined effect of water uptake, erosion, and interaction may result in prolonged drug release exceeding 24 h ^[121][195].

Chitosan is a cationic polymer derived from deacetylation of chitin, consisting of (1-4)-2-amino-2-deoxy-β-D-glucan. It possesses favourable processability and reactivity due to the presence of free hydroxyl and amino groups in its structure ^[122][196]. With its high hydrophilicity and semicrystalline nature, chitosan exhibits hydrogen bonding with water molecules, unlike many hydrocolloids that have anionic properties in aqueous environments. When chitosan is dissolved in acidic solutions, it becomes cationic and soluble. This leads to a strong attraction between chitosan and these hydrocolloids when they are blended together ^[123][197].

Furthermore, the results indicated that chitosan-λ-carrageenan-based matrices exhibited promise as controlled-release drug carriers due to their lower sensitivity to pH and ionic strength compared to chitosan-κ-carrageenan and chitosan-ι-carrageenan matrices ^[124][206]. Carrageenan maintains a certain degree of ionization even at low pH due to its low pKa value ^[125][207], making it suitable for the preparation of gastric floating tablets ^[126][208].