Current Pharmaceutical Design - Volume 25, Issue 11, 2019

Background: In recent decades, there has been an increased interest in the utilization of polysaccharides showing biological activity for various novel applications owing to their biocompatibility, biodegradability, non-toxicity, and some specific therapeutic activities. Increasing studies have started in the past few years to develop algal polysaccharides-based biomaterials for various applications. Methods: Saccharide mapping or enzymatic profiling plays a role in quality control of polysaccharides. Whereby, in vitro and in vivo tests as well as toxicity level discriminating polysaccharides biological activities. Extraction and purification methods are performed in obtaining algal derived polysaccharides followed by chromatographic profiles of their active compounds, structural features, physicochemical properties, and reported biological activities. Results: Marine algae are capable of synthesizing Glycosaminoglycans (GAGs) and non-GAGs or GAG mimetics such as sulfated glycans. The cell walls of algae are rich in sulfated polysaccharides, including alginate, carrageenan, ulvan and fucoidan. These biopolymers are widely used algal-derived polysaccharides for biological and biomedical applications due to their biocompatibility and availability. They constitute biochemical compounds that have multi-functionalization, therapeutic potential and immunomodulatory abilities, making them promising bioactive products and biomaterials with a wide range of biomedical applications. Conclusion: Algal-derived polysaccharides with clearly elucidated compositions/structures, identified cellular activities, as well as desirable physical properties have shown the potential that may create new opportunities. They could be maximally exploited to serve as therapeutic tools such as immunoregulatory agents or drug delivery vehicles. Hence, novel strategies could be applied to tailor multi-functionalization of the polysaccharides from algal species with vast biomedical application potentials.

Background: Pyropia (Porphyra), commonly known as nori or laver, is an important food source in many parts of the world. Edible dried Pyropia contains numerous nutrients and biofunctional components, including proteins, vitamins, eicosapentaenoic acid, minerals, carotenoids, mycosporine-like amino acids, and carbohydrate, and one of the compounds which we are interested in is porphyran, a sulfated polysaccharide comprising the hot-water-soluble portion of Pyropia cell walls. Researchers have performed a large number of in-depth studies on the biological activity and potential therapeutic applications of porphyrans and oligoporphyrans. Methods: This mini review aims to provide comprehensive and update overview on the source, extraction, structure, biological activities and structure-activity relationships of porphyrans and oligoporphyrans based on the studies in the past 30 years which were included in Web of Science. Results: The structure of porphyran has been basically determined given that its straight chain is relatively simple, and the skeleton structure has been described. The extraction methods were simplified continuously, but different extraction methods and post- processing methods still had great influence on the structure and composition of porphyran, so there was no standardized extraction process which can achieve quality control until now. In order to obtain oligoporphyrans, there are a variety of degradation methods, including chemical method, physical method and enzymatic method, but it is worth mentioning that specific degradation enzyme is still unavailable. Studies on the biological and pharmacology properties include antioxidant, anti-tumor, anti-inflammatory, immunomodulation, anti-cardiovascular and cerebrovascular diseases and drug delivery. Conclusion: Owing to the therapeutic potential and drug delivery applications, porphyran and oligoporphyrans are expected to be further developed as a medicine against human diseases, as well as a supplement in cosmetics and health products.

Background: With the advancement in the field of medical science, the idea of sustained release of the therapeutic agents in the patient’s body has remained a major thrust for developing advanced drug delivery systems (DDSs). The critical requirement for fabricating these DDSs is to facilitate the delivery of their cargos in a spatio-temporal and pharmacokinetically-controlled manner. Albeit the synthetic polymer-based DDSs normally address the above-mentioned conditions, their potential cytotoxicity and high cost have ultimately constrained their success. Consequently, the utilization of natural polymers for the fabrication of tunable DDSs owing to their biocompatible, biodegradable, and non-toxic nature can be regarded as a significant stride in the field of drug delivery. Marine environment serves as an untapped resource of varied range of materials such as polysaccharides, which can easily be utilized for developing various DDSs. Methods: Carrageenans are the sulfated polysaccharides that are extracted from the cell wall of red seaweeds. They exhibit an assimilation of various biological activities such as anti-thrombotic, anti-viral, anticancer, and immunomodulatory properties. The main aim of the presented review is threefold. The first one is to describe the unique physicochemical properties and structural composition of different types of carrageenans. The second is to illustrate the preparation methods of the different carrageenan-based macro- and micro-dimensional DDSs like hydrogels, microparticles, and microspheres respectively. Fabrication techniques of some advanced DDSs such as floating hydrogels, aerogels, and 3-D printed hydrogels have also been discussed in this review. Next, considerable attention has been paid to list down the recent applications of carrageenan-based polymeric architectures in the field of drug delivery. Results: Presence of structural variations among the different carrageenan types helps in regulating their temperature and ion-dependent sol-to-gel transition behavior. The constraint of low mechanical strength of reversible gels can be easily eradicated using chemical crosslinking techniques. Carrageenan based-microdimesional DDSs (e.g. microspheres, microparticles) can be utilized for easy and controlled drug administration. Moreover, carrageenans can be fabricated as 3-D printed hydrogels, floating hydrogels, and aerogels for controlled drug delivery applications. Conclusion: In order to address the problems associated with many of the available DDSs, carrageenans are establishing their worth recently as potential drug carriers owing to their varied range of properties. Different architectures of carrageenans are currently being explored as advanced DDSs. In the near future, translation of carrageenan-based advanced DDSs in the clinical applications seems inevitable.

Background: Recently, researchers have given more and more consideration to natural polysaccharides thanks to their huge properties such as stability, biodegradability and biocompatibility for food and therapeutics applications. Methods: a number of enzymatic and chemical processes were performed to generate bioactive molecules, such as low molecular weight fractions and oligosaccharides derivatives from algal polysaccharides. Results: These considerable characteristics allow algal polysaccharides and their derivatives such as low molecular weight polymers and oligosaccharides structures to have great potential to be used in lots of domains, such as pharmaceutics and agriculture etc. Conclusion: The present review describes the mains polysaccharides structures from Algae and focuses on the currents agricultural (fertilizer, bio-elicitor, stimulators, signaling molecules and activators) and pharmaceutical (wound dressing, tissues engineering and drugs delivery) applications by using polysaccharides and/or their oligosaccharides derivatives obtained by chemical, physical and enzymatic processes.

Background: Utilization of macroalgae has gained much attention in the field of pharmaceuticals, nutraceuticals, food and bioenergy. Macroalgae has been widely consumed in Asian countries as food from ancient days and proved that it has potential bioactive compounds which are responsible for its nutritional properties. Macroalgae consists of a diverse range of bioactive compounds including proteins, lipids, pigments, polysaccharides, etc. Polysaccharides from macroalgae have been utilized in food industries as gelling agents and drug excipients in the pharmaceutical industries owing to their biocompatibility and gel forming properties. Exploration of macroalgae derived sulfated polysaccharides in biomedical applications is increasing recently. Methods: In the current review, we have provided information of three different sulfated polysaccharides such as carrageenan, fucoidan and ulvan and their isolation procedure (enzymatic precipitation, microwave assisted method, and enzymatic hydrolysis method), structural details, and their biomedical applications exclusively for bone tissue repair and regeneration. Results: From the scientific results on sulfated polysaccharides from macroalgae, we conclude that sulfated polysaccharides have exceptional properties in terms of hydrogel-forming ability, scaffold formation, and mimicking the extracellular matrix, increasing alkaline phosphatase activity, enhancement of biomineralization ability and stem cell differentiation for bone tissue regeneration. Conclusion: Overall, sulfated polysaccharides from macroalgae may be promising biomaterials in bone tissue repair and regeneration.

Background: Algal polysaccharide and oligosaccharide derivatives have been shown to possess a variety of therapeutic potentials and drug delivery applications. Algal polysaccharides contain sulfated sugar monomers derived from seaweed including brown, red, and green microalgae. Here, in this review, the recent progress of algal polysaccharides’ therapeutic applications as anticancer agents, as well as underlying cellular and molecular mechanisms was investigated. Moreover, recent progress in the structural chemistry of important polysaccharides with anticancer activities were illustrated. Methods: Electronic databases including “Scopus”, “PubMed”, and “Cochrane library” were searched using the keywords “cancer”, or “tumor”, or “malignancy” in title/abstract, along with “algae”, or “algal” in the whole text until July 2018. Only English language papers were included. Results: The most common polysaccharides involved in cancer management were sulfated polysaccharides, Fucoidans, Carageenans, and Ulvan from different species of algae that have been recognized in vitro and in vivo. The underlying anticancer mechanisms of algal polysaccharides included induction of apoptosis, cell cycle arrest, modulation of transduction signaling pathways, suppression of migration and angiogenesis, as well as activation of immune responses and antioxidant system. VEGF/VEGFR2, TGFR/Smad/Snail, TLR4/ROS/ER, CXCL12/ CXCR4, TGFR/Smad7/Smurf2, PI3K/AKT/mTOR, PBK/TOPK, and β-catenin/Wnt are among the main cellular signaling pathways which have a key role in the preventive and therapeutic effects of algal polysaccharides against oncogenesis. Conclusion: Algal polysaccharides play a crucial role in the management of cancer and may be considered the next frontier in pharmaceutical research. Further well-designed clinical trials are mandatory to evaluate the efficacy and safety of algal polysaccharides in patients with cancer.

Background: Chronic skin wounds and pressure ulcers represent major health care problems in diabetic individuals, as well as patients who suffered a spinal cord injury. Current treatment methods are only partially effective and such wounds exhibit a high recurrence rate. Open wounds are at high risk of invasive wound infections, which can lead to amputation and further disability. An interdisciplinary approach is needed to develop new and more effective therapies. Methods: The purpose of this work is to review recent studies focusing on the use of algal polysaccharides in commercially available as well as experimental wound dressings. Studies that discuss wound dressings based on algal polysaccharides, some of which also contain growth factors and even living cells, were identified and included in this review. Results and Conclusion: Algal polysaccharides possess mechanical and physical properties, along with excellent biocompatibility and biodegradability that make them suitable for a variety of applications as wound dressings. Furthermore, algal polysaccharides have been used for a dual purpose, namely as wound covering, but also as a vehicle for drug delivery to the wound site.

Background: Solid free forming (SFF) technique also called additive manufacturing process is immensely popular for biofabrication owing to its high accuracy, precision and reproducibility. Method: SFF techniques like stereolithography, selective laser sintering, fused deposition modeling, extrusion printing, and inkjet printing create three dimension (3D) structures by layer by layer processing of the material. To achieve desirable results, selection of the appropriate technique is an important aspect and it is based on the nature of biomaterial or bioink to be processed. Result & Conclusion: Alginate is a commonly employed bioink in biofabrication process, attributable to its nontoxic, biodegradable and biocompatible nature; low cost; and tendency to form hydrogel under mild conditions. Furthermore, control on its rheological properties like viscosity and shear thinning, makes this natural anionic polymer an appropriate candidate for many of the SFF techniques. It is endeavoured in the present review to highlight the status of alginate as bioink in various SFF techniques.

Background: Imitating nature in the design of bio-inspired drug delivery systems resulted in several success stories. However, the practical application of biomimicry is still largely unrealized owing to the fact that we tend to copy the shape more often than the whole biology. Interesting chemistry of polysaccharides provides endless possibilities for drug complex formation and creation of delivery systems with diverse morphological and surface properties. However, the type of biological response, which may be induced by these systems, remains largely unexploited. Methods: Considering the most current research for the given topic, in this review, we will try to present the integrative approaches for the design of biomimetic DDS’s with improved therapeutic or theranostic effects based on different algal polysaccharides that exert multiple biological functions. Results: Algal polysaccharides may provide building blocks for bioinspired drug delivery systems capable of supporting the mechanical properties of nanomedicines and mimicking various biological processes by molecular interactions at the nanoscale. Numerous research studies demonstrate the efficacy and safety of multifunctional nanoparticles integrating several functions in one delivery system, composed of alginate, carrageenan, ulvan, fucoidan and their derivatives, intended to be used as bioartificial microenvironment or for diagnosis and therapy of different diseases. Conclusion: Nanodimensional structure of polysaccharide DDS’s shows substantial influence on the bioactive motifs potential availability for interaction with a variety of biomolecules and cells. Evaluation of the nano dimensional structure-activity relationship is crucial for unlocking the full potential of the future application of polysaccharide bio-mimicking DDS in modern diagnostic and therapeutic procedures.

Marine plants, animals and microorganisms display steady growth in the ocean and are abundant carbohydrate resources. Specifically, natural polysaccharides obtained from brown algae have been drawing increasing attention owing to their great potential in pharmaceutical applications. This review describes the structural and biological features of brown algal polysaccharides, including alginates, fucoidans, and laminarins, and it highlights recently developed approaches used to obtain the oligo- and polysaccharides with defined structures. Functional modification of these polysaccharides promotes their advanced applications in biomedical materials for controlled release and targeted drug delivery, etc. Moreover, brown algal polysaccharides and their derivatives possess numerous biological activities with anticancer, anticoagulant, wound healing, and antiviral properties. In addition, we also discuss carbohydrate- based substrates from brown algae, which are currently in clinical and preclinical studies, as well as the marine drugs that are already on the market. The present review summarizes the recent development in carbohydratebased products from brown algae, with promising findings that could rapidly facilitate the future discovery of novel marine drugs.

Nanotechnology refers to the control, manipulation, study and manufacture of structures and devices at the nanometer size range. The small size, customized surface, improved solubility and multi-functionality of nanoparticles will continue to create new biomedical applications, as nanoparticles allow to dominate stability, solubility and bioavailability, as well controlled release of drugs. The type of a nanoparticle, and its related chemical, physical and morphological properties influence its interaction with living cells, as well as determine the route of clearance and possible toxic effects. This field requires cross-disciplinary research and gives opportunities to design and develop multifunctional devices, which allow the diagnosis and treatment of devastating diseases. Over the past few decades, biodegradable polymers have been studied for the fabrication of drug delivery systems. There was extensive development of biodegradable polymeric nanoparticles for drug delivery and tissue engineering, in view of their applications in controlling the release of drugs, stabilizing labile molecules from degradation and site-specific drug targeting. The primary aim is to reduce dosing frequency and prolong the therapeutic outcomes. For this purpose, inert excipients should be selected, being biopolymers, e.g. sodium alginate, commonly used in controlled drug delivery. Nanoparticles composed of alginate (known as anionic polysaccharide widely distributed in the cell walls of brown algae which, when in contact with water, forms a viscous gum) have emerged as one of the most extensively characterized biomaterials used for drug delivery and targeting a set of administration routes. Their advantages include not only the versatile physicochemical properties, which allow chemical modifications for site-specific targeting but also their biocompatibility and biodegradation profiles, as well as mucoadhesiveness. Furthermore, mechanical strength, gelation, and cell affinity can be modulated by combining alginate nanoparticles with other polymers, surface tailoring using specific targeting moieties and by chemical or physical cross-linking. However, for every physicochemical modification in the macromolecule/ nanoparticles, a new toxicological profile may be obtained. In this paper, the different aspects related to the use of alginate nanoparticles for drug delivery and targeting have been revised, as well as how their toxicological profile will determine the therapeutic outcome of the drug delivery system.

Background: Over the past two decades, there have been substantial progress and a growing body of research on using natural polymeric biomaterials in emerging biomedical applications. Among different natural biopolymers, polysaccharides have gained considerable attraction among biomedical scientists and surgeons due to their biocompatibility, biodegradability, anti-inflammatory, and antimicrobial properties. In recent years, algalbased polysaccharides including agar, alginate, and carrageenan, have been broadly suggested for different biomedical applications. Methods: The aim of this paper is discussing various possible applications of algal-based polysaccharides in biomedical engineering particularly in controlled drug delivery systems. The main properties of each algal polysaccharide will be discussed, and particular drug delivery applications will be presented. Results: Algal polysaccharides can be detected in a group of photosynthetic unite as their key biomass constituents. They provide a range of variety in their size, shape, liquefaction, chemical stability, and crosslinking ability. In addition, algal polysaccharides have shown exceptional gelling properties including stimuli-responsive behavior, softness, and swelling properties. Conclusion: All the mentioned properties of alga polysaccharides lead to their successful usage in biomedical applications specially targeted and controlled drug delivery systems such as particles, capsules, and gels.