InTechOpen uses cookies to offer you the best online experience. By continuing to use our site, you agree to our Privacy Policy.

Agricultural and Biological Sciences » "Biological Activities and Application of Marine Polysaccharides", book edited by Emad A. Shalaby, ISBN 978-953-51-2860-1, Print ISBN 978-953-51-2859-5, Published: January 11, 2017 under CC BY 3.0 license. © The Author(s).

Chapter 7

Marine Polysaccharides as Multifunctional Pharmaceutical Excipients

By G. Thirumurugan and M.D. Dhanaraju
DOI: 10.5772/66191

Article top


The two rate-determining steps in the absorption of orally administered dosage form.
Figure 1. The two rate-determining steps in the absorption of orally administered dosage form.
Structure of cellulose, chitin and chitosan.
Figure 2. Structure of cellulose, chitin and chitosan.
Disintegrants facilitating the breakdown of the tablet into granules.
Figure 3. Disintegrants facilitating the breakdown of the tablet into granules.
Dissolution enhancer facilitating dissolution for the poor soluble drug.
Figure 4. Dissolution enhancer facilitating dissolution for the poor soluble drug.
Illustrating the mechanism of various marine polysaccharide carriers and their method of preparation.
Figure 5. Illustrating the mechanism of various marine polysaccharide carriers and their method of preparation.
Illustrating the mechanism of action involved in the pharmacological activity of marine polysaccharides.
Figure 6. Illustrating the mechanism of action involved in the pharmacological activity of marine polysaccharides.

Marine Polysaccharides as Multifunctional Pharmaceutical Excipients

G. Thirumurugan and M.D. Dhanaraju
Show details


This chapter is presented to depict the chance of marine polysaccharides satisfying the properties of good pharmaceutical excipients and the potential of that could be utilized as multifunctional pharmaceutical excipients in the pharmaceutical solid dosage form manufacturing as fillers, diluents/vehicles, binders, glidants, binders and disintegrants, and so on. In addition, this chapter discusses the use of marine polysaccharide holding a specific pharmacological activity in the formulation/dosage form, which is used for the same aliment/disease.

Keywords: marine polysaccharide, pharmaceutical excipients, bioavailability, drug delivery, dissolution, disintegrants, pharmacological activity

1. Introduction

Drugs, which are obtained from plants, animals, marine source or minerals, are not very often administered in their pure form. Before releasing into the market, these drugs are combined with a variety of inert substances (excipients/adjuvants) and modified into a dosage form, which is convenient to be administered by a specified route [1]. Similar to the drugs, these excipients are also obtained from many sources, namely natural, synthetic sources. Nowadays, the naturally obtained excipients have shown more interest due to the various advantages like low cost, biocompatibility, biodegradability, non-toxicity, easy availability, eco-friendly processing, superior patient tolerance and acceptance [2]. Before, it was thought that the therapeutic reaction to a drug is a characteristic of its inherent pharmacological action. However, nowadays, it is much implicit that the dose-response connection obtained after drug administration by various routes—for example, oral and parenteral—is not identical. The difference is also observed when the same medicine is administered as dissimilar dosage forms or similar formulations produced by dissimilar manufacturers, which in turn depends upon the physical, chemical properties of the drug, the excipients present in the formulation, the technique of formulation and the way of administration [1].

Natural marine origins are among the most widely used excipients in the formulation of different dosage forms. A number of marine-based polysaccharides, such as agar, alginate, carrageenan, fucoidan, chitosan and hyaluronan are utilized in pharmaceutical dosage form as binders, vehicles, disintegrating agents, gelling agents and drug release sustaining agents [3].

The purpose of this review is to discuss potential pharmaceutical formulation development applications of marine polysaccharides, with a special emphasis in multifunctional excipients development for enhancing bioavailability, drug delivery applications. In addition, this review discusses the use of marine polysaccharide holding a specific pharmacological activity in the formulation/dosage form, which is used for the same aliment/disease, for example, incorporating the marine polysaccharide having anti-cancer activity in anti-cancer drug formulation as excipients. In fact, data has added that such excipients operate on well-distinct biological pathways and receptors in order to implement their valuable properties. If additives that work on several cancer pharmacological pathways or receptors targets are jointed together in concentrations that are at and/or more than their recommended levels, then there is a possibility exists that such a formulated dosage form may offer “standalone” control of cancer.

2. Marine polysaccharides, as multifunctional pharmaceutical excipients

A drug injected intravascularly (I.V/I.A) directly enters the blood and produces its pharmacological effects. The majority of drugs are administered extravascularly, usually through oral route. If anticipated to act systemically, such drugs can produce their pharmacological actions only when they come into the blood circulation from their site of application. In order to reach the blood circulation, orally administered formulation must disintegrate, deaggregate and dissolution of the drug in the aqueous fluid at the absorption site must occur [4]. If the drugs are not hydrophilic in nature, the absorption process of drugs like these is usually dissolution rate-limited (Figure 1).


Figure 1.

The two rate-determining steps in the absorption of orally administered dosage form.

Better absorption can be achieved by altering the characteristics of the dosage form using pharmaceutical excipients. Moreover, pharmaceutical excipients help in the manufacturing process by serving as a binder, diluents, wetting agent, filling agent, disintegrating agents, dissolution enhancers, and so on. [3]. Now their increasing demands and expectations with regard to quality have stimulated the development of new additives characterized by advanced assay and lesser content of impurities. Quality of formulation does depend on the quality of excipient [4]. The purpose of this study is to give a scope for the researchers to try and develop a formulation that is made up of just the drug and natural marine polysaccharides. This review is done to depict the chance of some marine polysaccharides satisfying the properties of good pharmaceutical excipients if the stability of them has been explored sufficiently.

2.1. As binder

Marine polysaccharides can serve as a good binder in the production of tablets by the wet granulation method of manufacture. In this role, binders are either added as a solution or as a solid into the powder mix (following which the granulating fluid, typically water, is added). Due to the high concentration of hydroxyl groups in the polysaccharide, generally have a high water-binding capacity that makes wet granulation easier [5]. The responsible bio-adhesives marine polysaccharides have extraordinarily high cohesive strength and binding strength to the solid surfaces, enabling the API to remain attached under tensional conditions.

2.2. As diluents

Marine polysaccharides can be employed as diluents/fillers in the formulation of tablets (by all methods) to increase the mass of the solid dosage forms that hold a low concentration of therapeutic agent and thereby render the manufacturing process more reliable and reproducible [6]. For example, chitin and chitosan are used as a diluent or filler and as a binder in direct compression of tablet processing, as a disintegrant, and so on. Chitin and chitosan have a lowest bulk and tapped density that cause good flow as well as compaction during filling and tablet compression processing. Figure 2 shows the structure of cellulose chitin and chitosan.


Figure 2.

Structure of cellulose, chitin and chitosan.

2.3. As disintegrants

Disintegrants are materials added to the dosage forms that enhance the breakup or disintegration of tablet formulations into smaller particles that dissolve faster than in the absence of disintegrants. These materials have the main role to oppose the efficiency of tablet binder and physical forces that behave under compression to form the tablets. Tablet disintegrant usually considered as the rate determining step (RDS) in a faster drug release. Marine polysaccharides may behave as a good disintegrating agent by increasing the porosity, wettability and wicking or capillary action and operate by swelling in the presence of aqueous fluids in tablet formulations to facilitate the breakdown of the tablet into granules upon entry into the stomach [7] (Figure 3).


Figure 3.

Disintegrants facilitating the breakdown of the tablet into granules.

2.4. As dissolution enhancers

Marine polysaccharides may serve as a dissolution enhancer for the poor soluble drug. These powders can reduce cohesive forces holding a tablet dosage form together and induce the breakup into smaller granules, thus increasing the effective surface area for dissolution (Figure 4).


Figure 4.

Dissolution enhancer facilitating dissolution for the poor soluble drug.

2.5. As drug delivery carriers

Marine polysaccharides have been widely used to synthesize drug delivery carriers. They are bio-compatible, non-toxic and bio-degradable and stimuli-responsive makes marine polysaccharides appropriate sources for the building of complex loading devices with a release that can be effectively controlled [4]. Table 1 shows the compilation of marine polysaccharides utilized as drug delivery carriers, and Figure 5 illustrates the mechanisms of various marine polysaccharide carriers and its method of preparation.

S. noName of marine polysaccharideSourceDrug delivery use
Brown sea weedExcipient, stabilizer [8], hydrogel matrices, beads, particles [912], micro particles [13, 14]
Red algaeTablet compressor [15], controlled release (temperature sensitive) [16], |fast release [17], sustained release [18] (Ph sensitive)
Brown algaeMicrospores, fucospheres [19], insulin controlled release [20], nano-particles [21]
Green algaeCosmetic delivery [22], nano-fibres (tissue engineering and regenerative medicine) [23], hydrogel [24]
Marine animal (chitin)Nano particles, beads of capsules for controlled release, membranes, films and scaffolds for tissue engineering and regenerative medicine [25], stabilization, acceleration (release), sustained release [26]
Marine animal (glycosaminoglycans)Hydrogels [27], micro [28], nano particles [29], coating material [30], liposomes [31]
7.Chondroitin sulfate
Marine animals (whale and shark)Controlled release [32], anti-cancer drug delivery [33]
8.Dermatan sulfate
Ray skin (glycosaminoglycans)Stabilizer for growth factor, cytokines [34]
9.Heparan sulfate
Ray skin (glycosaminoglycans)Cancer treatment [35]
10.Keratan sulfate
Ray skin (glycosaminoglycans)
Red algaeHydrogels [36]

Table 1.


Compilation of marine polysaccharides utilized as drug delivery carriers.


Figure 5.

Illustrating the mechanism of various marine polysaccharide carriers and their method of preparation.

Drug delivery devices can be constructed using various methods and can be synthesized in a variety of shapes, such as hydro gels, micro or nanoparticles and capsules, capable of protecting a variety of bioactive agents such as proteins and nucleic acids.

3. Pharmacological activity of marine polysaccharides and potential possibilities of standalone effects when incorporating as excipients

Marine polysaccharides stand for a number of abundant bio-active substances in marine organisms. In fact, numerous marine macro- and microorganisms are good quality possessions of carbohydrates with miscellaneous applications due to their bio-functional efficacies. By involving on cell propagation and cycle, and by modulating metabolic pathways, marine polysaccharides have numerous pharmacological efficacies, such as antioxidative, antibacterial, antiviral, immuno-stimulatory, anticoagulant and anticancer effects. Besides the polysaccharides, monosaccharides are useful for humans and can cure many diseases, mainly those linked to metabolism deficiency such as diabetes.

There has been growing facts in recent years that pharmaceutical additives may not be harmless, “inert” components of a formulation, but may hold either “stand alone” pharmacological activity or may act to modify the pharmacological efficacy of the API. Because most excipients have historically derived from food or food products, they have been assigned—and in most cases, experimentally confirmed—to have widespread pharmacological activity based on the ingestion of those products. Marine polysaccharides holding a specific pharmacological activity can be incorporated as an excipient in the formulation/dosage form, which is used for the same aliment/disease. Table 2 shows the pharmacological activity of marine polysaccharides, and Figure 6 illustrates the mechanism of action involved in the pharmacological activity of marine polysaccharides.

S. noMarine polysaccharideSourcePharmacological activity
1.AlginateBrown sea weed
2.CarrageenansRed algaeAnticoagulant [37], Anti-tumour [38] , Immuno-modulator [39], anti-hyperlipidaemic [40], Antioxidant [41], Antibacterial, viral [42], bird flu, dengue, Hepatitis A, HIV [43]
3.FucoidansBrown algaeAnti-tumour [44, 45], anti-thrombin [19], anti-coagulant, anti-inflammatory, anti-adhesive and anti-viral [46], burn treatment [47]
4.UlvansGreen algaeAnti-viral, anti-oxidant, anti-coagulant, anti-tumour, anti-hyperlipidaemic and immune system enhancer [48]
5.ChitosansMarine animal (chitin)Antimicrobial [49], anti-tumour and inflammatory [50]
6.HyaluronansMarine animal (glycosaminoglycans)Wound treatment [51], supplement for arthritis [52]
7.Chondroitin sulfateMarine animals (whale and shark)Anti-coagulant [53], supplement for arthritis [53]
8.Dermatan sulfateRay skin (glycosaminoglycans)Anti-coagulant [54]
9.Heparan sulfateRay skin (glycosaminoglycans)
10.Keratan sulfateRay skin (glycosaminoglycans)Anti-adhesive, osteoarthritis [54]
11.AgaroseRed algaeGlucose intolerance in type 2 diabetes mellitus, weight loss, anti-bacterial [40]

Table 2.


Pharmacological activity of marine polysaccharides.


Figure 6.

Illustrating the mechanism of action involved in the pharmacological activity of marine polysaccharides.

However, the majority of the pathways or modes of action has not been revealed in humans. In addition, fairly only some have been investigated in-vitro. These in-vitro findings are unable to extrapolate into their actions in-vivo in humans. There should be well-controlled human clinical investigations using such a mixture of additives are essential prior to any rationalization for effectiveness can be asserted.

Ideation of using “marine polysaccharide bio-active excipients” is possible for diseases that are chronic in nature and for whom gradual and lasting beneficial efficacy may be observed from the modulation of signalling pathways that direct to incremental but visible improvements in the quality of life. Such “marine polysaccharide bio-active excipients” may not be efficient for acute diseases for which radical interventions are necessary.

4. Conclusion

Marine polysaccharides have a huge potential as multifunctional pharmaceutical excipients for commercial needs. However, there is a need to characterize, check compatibility of these polysaccharides to produce pharmaceutical grade additives that could find the utility in drug dosage form. In addition, research is warranted in pharmacodynamic interaction of these marine polysaccharides and particular drug when using for same aliments.


1 - Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics: A Treatise. 1st ed. Delhi: Vallabh Prakashan Publishers; 1995, pp. 296–297.
2 - Ramachandran S, Shaheedha SM, Thirumurugan G and Dhanaraju MD. Floating controlled drug delivery system of famotidine loaded hollow microspheres (microballoons) in the stomach. Current Drug Delivery. 2010;7(1):93–97. doi: 10.2174/156720110790396436
3 - Saravanan M, Bhaskar K, Srinivasa Rao G, Dhanaraju MD. Ibuprofen-loaded ethylcellulose/polystyrene microspheres: An approach to get prolonged drug release with reduced burst effect and low ethylcellulose content. Journal of Microencapsulation: Micro and Nano Carriers. 2003;20(3)289–302. doi:10.1080/0265204031000093087
4 - Dhanaraju MD, Elisabeth S, Thirumurugan G. Triamcinolone-loaded glutaraldehyde cross-linked chitosan microspheres: Prolonged release approach for the treatment of rheumatoid arthritis. Drug Delivery. 2011;18(3):198–207. doi:10.3109/10717544.2010.528069
5 - Paolucci M, Fasulo G, Volpe MG. Employment of marine polysaccharides to manufacture functional biocomposites for aquaculture feeding applications. Marine Drugs. 2015;13(5):2680–2693. doi:10.3390/md13052680.
6 - De Jesus Raposo MF, de Morais AMB, de Morais RMSC. Marine polysaccharides from algae with potential biomedical applications. Marine Drugs. 2015;13(5):2967–3028. doi:10.3390/md13052967.
7 - Thomas NV, Kim S-K. Beneficial effects of marine algal compounds in cosmeceuticals. Marine Drugs. 2013;11(1):146–164. doi:10.3390/md11010146.
8 - Mano J.F. Stimuli-responsive polymeric systems for biomedical applications. Advanced Engineering Materials. 2008;10:515–527. doi: 10.1002/adem.200700355.
9 - Laurienzo P. Marine polysaccharides in pharmaceutical applications: An Overview. Marine Drugs. 2010;8:2435–2465. doi: 10.3390/md8092435.
10 - Gombotz WR, Wee SF. Protein release from alginate matrices. Advanced Drug Delivery Review. 2012;64:194–205. doi: 10.1016/j.addr.2012.09.007.
11 - Beneke CE, Viljoen AM, Hamman JH. Polymeric plant-derived excipients in drug delivery. Molecules. 2009;14:2602–2620. doi: 10.3390/molecules14072602.
12 - Sudhakar Y, Kuotsu K, Bandyopadhyay AK. Buccal bioadhesive drug delivery: A promising option for orally less efficient drugs. Journal of Controlled Release. 2006;114:15–40. doi: 10.1016/j.jconrel.2006.04.012.
13 - Lima AC, Sher P, Mano JF. Production methodologies of polymeric and hydrogel particles for drug delivery applications. Expert Opinion on Drug Delivery. 2012;9:231–248. doi: 10.1517/17425247.2012.652614.
14 - Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices. Journal of Controlled Release. 2001;70:1–20. doi: 10.1016/S0168-3659(00)00339-4.
15 - Picker KM. Matrix tablets of carrageenans. I. A compaction study. Drug Development and Industrial Pharmacy. 1999;25:329–337. doi: 10.1081/DDC-100102178.
16 - Ganta S, Devalapally H, Shahiwala A, Amiji M. A review of stimuli-responsive nanocarriers for drug and gene delivery. Journal of Controlled Release 2008;126:187–204. doi: 10.1016/j.jconrel.2007.12.017.
17 - Bornhoft M, Thommes M, Kleinebudde P. Preliminary assessment of carrageenan as excipient for extrusion/spheronisation. European Journal of Pharmaceutics and Biopharmaceutics. 2005;59:127–131. doi: 10.1016/j.ejpb.2004.05.007.
18 - Bonferoni MC, Rossi S, Ferrari F, Bertoni M, Bolhuis GK, Caramella C. On the employment of lambda carrageenan in a matrix system. III. Optimization of a lambda carrageenan-HPMC hydrophilic matrix. Journal of Controlled Release. 1998;51:231–239. doi: 10.1016/S0168-3659(97)00175-2.
19 - Sezer AD, Akbuga J. Fucosphere: New microsphere carriers for peptide and protein delivery: Preparation and in vitro characterization. Journal of Microencapsulation. 2006;23:513–522. doi: 10.1080/02652040600687563.
20 - Sato K, Takahashi S, Anzai J. Layer-by-layer thin films and microcapsules for biosensors and controlled release. Analytical Sciences. 2012;28:929–938. doi: 10.2116/analsci. 28.929.
21 - Pinheiro AC, Bourbon AI, Cerqueira MA, Maricato E, Nunes C, Coimbra MA, Vicente AA. Chitosan/fucoidan multilayer nanocapsules as a vehicle for controlled release of bioactive compounds. Carbohydrate Polymer. 2015;115:1–9. doi: 10.1016/j.carbpol.2014.07.016.
22 - Ahmed OM, Ahmed RR. Anti-proliferative and apoptotic efficacies of ulvan polysaccharides against different types of carcinoma cells in vitro and in vivo. Journal of Cancer Science & Therapy. 2014;6:202–208. doi: 10.4172/1948-5956.1000272.
23 - Alves A, Sousa RA, Reis RL. A practical perspective on ulvan extracted from green algae. Journal of Applied Phycology. 2013;25:407–424. doi: 10.1007/s10811-012-9875-4.
24 - Morelli A, Chiellini F. Ulvan as a new type of biomaterial from renewable resources: Functionalization and hydrogel preparation. Macromolecular Chemistry and Physics. 2010;211:821–832. doi: 10.1002/macp.200900562.
25 - Prabaharan M, Mano JF. Chitosan-based particles as controlled drug delivery systems. Drug Delivery. 2005;12:41–57. doi: 10.1080/10717540590889781.
26 - Felt O, Buri P, Gurny R. Chitosan: A unique polysaccharide for drug delivery. Drug Development and Industrial Pharmacy. 1998;24:979–993. doi: 10.3109/03639049809089942.
27 - Santos JR, Alves NM, Mano JF. New thermo-responsive hydrogels based on poly (N-isopropylacrylamide)/hyaluronic acid semi-interpenetrated polymer networks: Swelling properties and drug release studies. Journal of Bioactive and Compatible Polymers. 2010;25:169–184. doi: 10.1177/0883911509357863.
28 - Lim ST, Martin GP, Berry DJ, Brown MB. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. Journal of Controlled Release. 2000;66:281–292. doi: 10.1016/S0168-3659(99)00285-0.
29 - Oyarzun-Ampuero FA, Brea J, Loza MI, Torres D, Alonso MJ. Chitosan-hyaluronic acid nanoparticles loaded with heparin for the treatment of asthma. International Journal of Pharmaceutics. 2009;381:122–129. doi: 10.1016/j.ijpharm.2009.04.009.
30 - Grech JMR, Mano JF, Reis RL. Chitosan beads as templates for layer-by-layer assembly and their application in the sustained release of bioactive agents. Journal of Bioactive and Compatible Polymers. 2008;23:367–380. doi: 10.1177/0883911508093389.
31 - Simoes S, Moreira JN, Fonseca C, Duzgunes N, de Lima MC. On the formulation of pH-sensitive liposomes with long circulation times. Advanced Drug Delivery Review. 2004;56:947–965. doi: 10.1016/j.addr.2003.10.038.
32 - Santo VE, Gomes ME, Mano JF, Reis RL. Chitosan-chondroitin sulphate nanoparticles for controlled delivery of platelet lysates in bone regenerative medicine. Journal of Tissue Engineering and Regenerative Medicine. 2012;6:S47–S59. doi: 10.1002/term.1519.
33 - Guo YM, Shi XM, Fang QL, Zhang J, Fang H, Jia WL, Yang G, Yang L. Facile preparation of hydroxyapatite-chondroitin sulfate hybrid mesoporous microrods for controlled and sustained release of antitumor drugs. Materials Letters. 2014;125:111–115. doi: 10.1016/j.matlet.2014.03.084.
34 - Vitale C, Berutti S, Bagnis C, Soragna G, Gabella P, Fruttero C, Marangella M. Dermatan sulfate: An alternative to unfractionated heparin for anticoagulation in hemodialysis patients. Journal of Nephrology. 2013;26:158–163. doi: 10.5301/jn.5000105.
35 - Knelson EH, Nee JC, Blobe GC. Heparan sulfate signaling in cancer. Trends in Biochemical Sciences. 2014;39:277–288. doi: 10.1016/j.tibs.2014.03.001.
36 - Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer. 2008;49:1993–2007. doi: 10.1016/j.polymer.2008.01.027.
37 - Silva FRF, Dore CMPG, Marques CT, Nascimento MS, Benevides NMB, Rocha HAO, Chavante SF, Leite EL. Anticoagulant activity, paw edema and pleurisy induced carrageenan: Action of major types of commercial carrageenans. Carbohydrate Polymers. 2010;79:26–33. doi: 10.1016/j.carbpol.2009.07.010.
38 - Zhou G, Sun Y, Xin H, Zhang Y, Li Z, Xu Z. In vivo antitumor and immunomodulation activities of different molecular weight lambda-carrageenans from Chondrus ocellatus. Pharmacological Research. 2004;50:47–53. doi: 10.1016/j.phrs.2003.12.002.
39 - Panlasigui LN, Baello OQ, Dimatangal JM, Dumelod BD. Blood cholesterol and lipid-lowering effects of carrageenan on human volunteers. Asia Pacific Journal of Clinical Nutrition. 2003;12:209–214.
40 - De Souza MCR, Marques CT, Dore CMG, da Silva FRF, Rocha HAO, Leite EL. Antioxidant activities of sulfated polysaccharides from brown and red seaweeds. Journal of Applied Phycology. 2007;19:153–160. doi: 10.1007/s10811-006-9121-z.
41 - Carlucci MJ, Ciancia M, Matulewicz MC, Cerezo AS, Damonte EB. Antiherpetic activity and mode of action of natural carrageenans of diverse structural types. Antiviral Research. 1999;43:93–102. doi: 10.1016/S0166-3542(99)00038-8.
42 - Schaeffer DJ, Krylov VS. Anti-HIV activity of extracts and compounds from algae and cyanobacteria. Ecotoxicology Environment Safety. 2000;45:208–227. doi: 10.1006/eesa.1999.1862.
43 - Ermakova S, Sokolova R, Kim SM, Um BH, Isakov V, Zvyagintseva T. Fucoidans from brown seaweeds sargassum hornery, eclonia cava, costaria costata: Structural characteristics and anticancer activity. Applied Biochemistry and Biotechnology. 2011;164:841–850. doi: 10.1007/s12010-011-9178-2.
44 - Anastyuk SD, Shevchenko NM, Ermakova SP, Vishchuk OS, Nazarenko EL, Dmitrenok PS, Zvyagintseva TN. Anticancer activity in vitro of a fucoidan from the brown alga fucus evanescens and its low-molecular fragments, structurally characterized by tandem mass-spectrometry. Carbohydrate Polymers. 2012;87:186–194. doi: 10.1016/j.carbpol.2011.07.036.
45 - Kim SK, Ravichandran YD, Khan SB, Kim YT. Prospective of the cosmeceuticals derived from marine organisms. Biotechnology and Bioprocess Engineering. 2008;13:511–523. doi: 10.1007/s12257-008-0113-5.
46 - Alves A, Sousa RA, Reis RL. In vitro cytotoxicity assessment of ulvan, a polysaccharide extracted from green algae. Phytotherapy Research. 2013;27:1143–1148. doi: 10.1002/ptr.4843.
47 - Rabea EI, Badawy ME, Stevens CV, Smagghe G, Steurbaut W. Chitosan as antimicrobial agent: Applications and mode of action. Biomacromolecules. 2003;4:1457–1465. doi: 10.1021/bm034130m.
48 - Qin CQ, Du YM, Xiao L, Li Z, Gao XH. Enzymic preparation of water-soluble chitosan and their antitumor activity. International Journal of Biological Macromolecules. 2002;31:111–117. doi: 10.1016/S0141-8130(02)00064-8.
49 - Chen WY, Abatangelo G. Functions of hyaluronan in wound repair. Wound Repair Regen.1999;7:79–89. doi: 10.1046/j.1524-475X.1999.00079.x.
50 - Jiang GB, Quan D, Liao K, Wang H. Novel polymer micelles prepared from chitosan grafted hydrophobic palmitoyl groups for drug delivery. Molecular Pharmaceutics. 2006;3:152–160. doi: 10.1021/mp050010c.
51 - Teien AN, Abildgaard U, Hook M. The anticoagulant effect of heparan sulfate and dermatan sulfate. Thrombosis Research. 1976;8:859–867. doi: 10.1016/0049-3848(76)90014-1.
52 - Wang DA, Varghese S, Sharma B, Strehin I, Fermanian S, Gorham J, Fairbrother DH, Cascio B, Elisseeff JH. Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. Nature Materials. 2007;6:385–392. doi: 10.1038/nmat1890.
53 - Mourao PA, Pereira MS. Searching for alternatives to heparin: Sulfated fucans from marine invertebrates. Trends in Cardiovascular Medicine. 1999;9:225–232. doi: 10.1016/S1050-1738(00)00032-3.
54 - Funderburgh JL. Keratan sulfate biosynthesis. IUBMB Life. 2002;54:187–194. doi: 10.1080/15216540214932.