The Safety Properties of Sodium Alginate and its Derivatives
DOI:
https://doi.org/10.14738/bjhmr.111.16126Abstract
Alginate is a biomaterial with a vast use in biomedicine, food and pharmaceutical industry due to its advantageous properties such as abundance, biocompatibility and easiness of gelation. The Food and Drug Administration (FDA) has confirmed some alginates salts and related derivative to “generally regarded as safe” components for oral use. According to the vast use of alginate as a harmless agent in food and pharmaceutical industries, logically its hydrolysate and ultimately its residues including Mannuronic and Guluronic acids, as alginate hydrolysate components are safe and non-toxic ingredients. In this regard, a number of studies have been conducted to reveal the safety of these agents. Hear, we aimed to review the safety of sodium alginate and its hydrolysate in the literature. In conclusion, the outcomes of acute and chronic toxicity studies indicate that the sodium alginate and its hydrolysate have a high safety profile when administered orally to animals.
References
Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Prog Polym Sci. 2012;37(1):106-26.
Bemiller JN, editor Structure‐property correlations of non‐starch food polysaccharides. Macromolecular symposia; 1999: Wiley Online Library.
Draget KI, Smidsrød O, Skjåk-Bræk G. Alginates from Algae. Biopolymers Online.
Ertesvåg H, Høidal HK, Hals IK, Rian A, Doseth B, Valla S. A family of modular type mannuronan C-5-epimerase genes controls alginate structure in Azotobacter vinelandii. Mol Microbiol. 1995;16(4):719-31.
Grasdalen H, Larsen B, Smidsrød O. 13C-N.m.r. studies of alginate. Carbohydrate Research. 1977;56(2):C11-C5.
Skjåk-Bræk G, Draget KI. 10.10 - Alginates: Properties and Applications. In: Matyjaszewski K, Möller M, editors. Polymer Science: A Comprehensive Reference. Amsterdam: Elsevier; 2012. p. 213-20.
Peteiro C. Alginate Production from Marine Macroalgae, with Emphasis on Kelp Farming. In: Rehm BHA, Moradali MF, editors. Alginates and Their Biomedical Applications. Singapore: Springer Singapore; 2018. p. 27-66.
Andriamanantoanina H, Rinaudo M. Relationship between the molecular structure of alginates and their gelation in acidic conditions. Polymer International. 2010;59(11):1531-41.
Andriamanantoanina H, Rinaudo M. Characterization of the alginates from five madagascan brown algae. Carbohydrate Polymers. 2010;82(3):555-60.
Gomez CG, Pérez Lambrecht MV, Lozano JE, Rinaudo M, Villar MA. Influence of the extraction-purification conditions on final properties of alginates obtained from brown algae (Macrocystis pyrifera). International journal of biological macromolecules. 2009;44(4):365-71.
Rehm BHA, Valla S. Bacterial alginates: biosynthesis and applications. Applied Microbiology and Biotechnology. 1997;48(3):281-8.
Sachan NK, Pushkar S, Jha A, Bhattcharya A. Sodium alginate: the wonder polymer for controlled drug delivery. J Pharm Res. 2009;2(8):1191-9.
Cable C. Sodium alginate. Handbook of pharmaceutical excipients. 2006;6.
Remminghorst U, Rehm BH. Bacterial alginates: from biosynthesis to applications. Biotechnology letters. 2006; 28:1701-12.
Chee S-Y, Wong P-K, Wong C-L. Extraction and characterisation of alginate from brown seaweeds (Fucales, Phaeophyceae) collected from Port Dickson, Peninsular Malaysia. Journal of Applied Phycology. 2011;23(2):191-6.
Vauchel P, Arhaliass A, Legrand J, Kaas R, Baron R. DECREASE IN DYNAMIC VISCOSITY AND AVERAGE MOLECULAR WEIGHT OF ALGINATE FROM LAMINARIA DIGITATA DURING ALKALINE EXTRACTION1. Journal of Phycology. 2008;44(2):515-7.
Sun J, Tan H. Alginate-based biomaterials for regenerative medicine applications. Materials. 2013;6(4):1285-309.
Kontominas MG. Use of alginates as food packaging materials. MDPI; 2020. p. 1440.
Ruocco N, Costantini S, Guariniello S, Costantini M. Polysaccharides from the marine environment with pharmacological, cosmeceutical and nutraceutical potential. Molecules. 2016;21(5):551.
Solah VA, Kerr DA, Adikara CD, Meng X, Binns CW, Zhu K, et al. Differences in satiety effects of alginate-and whey protein-based foods. Appetite. 2010;54(3):485-91.
Yao J, Zhou Y, Chen X, Ma F, Li P, Chen C. Effect of sodium alginate with three molecular weight forms on the water holding capacity of chicken breast myosin gel. Food Chemistry. 2018; 239:1134-42.
Szekalska M, Puciłowska A, Szymańska E, Ciosek P, Winnicka K. Alginate: current use and future perspectives in pharmaceutical and biomedical applications. International Journal of Polymer Science.
Sanchez-Ballester NM, Bataille B, Soulairol I. Sodium alginate and alginic acid as pharmaceutical excipients for tablet formulation: Structure-function relationship. Carbohydrate Polymers. 2021; 270:118399.
Gomez d’Ayala G, Malinconico M, Laurienzo P. Marine derived polysaccharides for biomedical applications: chemical modification approaches. Molecules. 2008;13(9):2069-106.
Kaneko K, Kanada K, Yamada T, MIYAGI M, SAITO N, OZEKI T, et al. Application of gel formation for taste masking. Chemical and pharmaceutical bulletin. 1997;45(6):1063-8.
Schmid W, Picker-Freyer KM. Tableting and tablet properties of alginates: characterisation and potential for soft tableting. European journal of pharmaceutics and biopharmaceutics. 2009;72(1):165-72.
Al-Khattawi A, Mohammed AR. Compressed orally disintegrating tablets: excipients evolution and formulation strategies. Expert opinion on drug delivery. 2013;10(5):651-63.
Koo OM. Pharmaceutical excipients: properties, functionality, and applications in research and industry: John Wiley & Sons; 2016.
Shah H, Jain A, Laghate G, Prabhudesai D. Pharmaceutical excipients. Remington: Elsevier; 2021. p. 633-43.
Jiang Y, Yu G, Zhou Y, Liu Y, Feng Y, Li J. Effects of sodium alginate on microstructural and properties of bacterial cellulose nanocrystal stabilized emulsions. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2020; 607:125474.
Acevedo-Fani A, Soliva-Fortuny R, Martín-Belloso O. Nanoemulsions as edible coatings. Current Opinion in Food Science. 2017; 15:43-9.
Gundewadi G, Rudra SG, Sarkar DJ, Singh D. Nanoemulsion based alginate organic coating for shelf-life extension of okra. Food Packaging and Shelf Life. 2018; 18:1-12.
Arroyo BJ, Bezerra AC, Oliveira LL, Arroyo SJ, Melo EA, Santos AMP. Antimicrobial active edible coating of alginate and chitosan add ZnO nanoparticles applied in guavas (Psidium guajava L.). Food Chem. 2020; 309:125566.
Martău GA, Mihai M, Vodnar DC. The Use of Chitosan, Alginate, and Pectin in the Biomedical and Food Sector-Biocompatibility, Bioadhesiveness, and Biodegradability. Polymers. 2019;11(11).
Bilal M, Iqbal HMN. Naturally-derived biopolymers: Potential platforms for enzyme immobilization. International journal of biological macromolecules. 2019; 130:462-82.
Makaremi M, Yousefi H, Cavallaro G, Lazzara G, Goh CBS, Lee SM, et al. Safely dissolvable and healable active packaging films based on alginate and pectin. Polymers. 2019;11(10):1594.
Najafi-Soulari S, Shekarchizadeh H, Kadivar M. Encapsulation optimization of lemon balm antioxidants in calcium alginate hydrogels. Journal of Biomaterials science, Polymer edition. 2016;27(16):1631-44.
Sohail A, Turner MS, Coombes A, Bostrom T, Bhandari B. Survivability of probiotics encapsulated in alginate gel microbeads using a novel impinging aerosols method. International Journal of Food Microbiology. 2011;145(1):162-8.
Heidebach T, Först P, Kulozik U. Microencapsulation of probiotic cells for food applications. Critical reviews in food science and nutrition. 2012;52(4):291-311.
Li A, Gong T, Hou Y, Yang X, Guo Y. Alginate-stabilized thixotropic emulsion gels and their applications in fabrication of low-fat mayonnaise alternatives. International journal of biological macromolecules. 2020; 146:821-31. URL: http://dx.doi.org/10.14738/bjhmr.111.16126. 271
Yang X, Li A, Yu W, Li X, Sun L, Xue J, et al. Structuring oil-in-water emulsion by forming egg yolk/alginate complexes: Their potential application in fabricating low-fat mayonnaise-like emulsion gels and redispersible solid emulsions. International journal of biological macromolecules. 2020; 147:595-606.
Georg Jensen M, Kristensen M, Astrup A. Effect of alginate supplementation on weight loss in obese subjects completing a 12-wk energy-restricted diet: a randomized controlled trial. The American journal of clinical nutrition. 2012;96(1):5-13.
Wilcox MD, Chater PI, Stanforth KJ, Woodcock AD, Dettmar PW, Pearson JP. The rheological properties of an alginate satiety formulation in a physiologically relevant human model gut system. Annals of Esophagus. 2022.
Guo L, Goff HD, Xu F, Liu F, Ma J, Chen M, et al. The effect of sodium alginate on nutrient digestion and metabolic responses during both in vitro and in vivo digestion process. Food Hydrocolloids. 2020; 107:105304.
Kothale D, Verma U, Dewangan N, Jana P, Jain A, Jain D. Alginate as promising natural polymer for pharmaceutical, food, and biomedical applications. Current drug delivery. 2020;17(9):755-75.
Sosnik A. Alginate particles as platform for drug delivery by the oral route: state-of-the-art. International Scholarly Research Notices. 2014;2014.
Coşkun G, Karaca E, Ozyurtlu M, Özbek S, Yermezler A, Çavuşoğlu İ. Histological evaluation of wound healing performance of electrospun poly (vinyl alcohol)/sodium alginate as wound dressing in vivo. Bio-Medical Materials and Engineering. 2014;24(2):1527-36.
Chang AA, Reuther MS, Briggs KK, Schumacher BL, Williams GM, Corr M, et al. In vivo implantation of tissue-engineered human nasal septal neocartilage constructs: a pilot study. Otolaryngology--Head and Neck Surgery. 2012;146(1):46-52.
Vériter S, Mergen J, Goebbels R-M, Aouassar N, Grégoire C, Jordan B, et al. In vivo selection of biocompatible alginates for islet encapsulation and subcutaneous transplantation. Tissue Engineering Part A. 2010;16(5):1503-13.
Lin H-R, Sung K, Vong W-J. In situ gelling of alginate/pluronic solutions for ophthalmic delivery of pilocarpine. Biomacromolecules. 2004;5(6):2358-65.
Sarei F, Dounighi NM, Zolfagharian H, Khaki P, Bidhendi SM. Alginate nanoparticles as a promising adjuvant and vaccine delivery system. Indian Journal of Pharmaceutical Sciences. 2013;75(4):442.
Generally Recognized as Safe (Internet), “U.S. Food and Drug Administration,” http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/SCOGS/ucm260857.htm.
Otterlei M, Østgaard K, Skjåk-Bræk G, Smidsrød O, Soon-Shiong P, Espevik T. Induction of cytokine production from human monocytes stimulated with alginate. Journal of Immunotherapy. 1991;10(4):286-91.
Ménard M, Dusseault J, Langlois G, Baille WE, K. Tam S, Yahia LH, et al. Role of protein contaminants in the immunogenicity of alginates. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2010;93(2):333-40.
Greco M, Saez CA, Brown MT, Bitonti MB. A simple and effective method for high quality co-extraction of genomic DNA and total RNA from low biomass Ectocarpus siliculosus, the model brown alga. PLoS One. 2014;9(5): e96470.
Nazeri S, Khadem Azarian S, Fattahi MJ, Sedaghat R, Tofighi Zavareh F, Aghazadeh Z, et al. Preclinical and pharmacotoxicology evaluation of α-l-guluronic acid (G2013) as a non-steroidal anti-inflammatory drug with immunomodulatory property. Immunopharmacology and Immunotoxicology. 2017;39(2):59-65.
Taeb M, Mortazavi-Jahromi SS, Jafarzadeh A, Mirzaei MR, Mirshafiey A. An in vitro evaluation of anti-aging effect of guluronic acid (G2013) based on enzymatic oxidative stress gene expression using healthy individuals PBMCs. Biomedicine & Pharmacotherapy. 2017; 90:262-7.
Hassani S, Afshari JT, Jafarnezhad-Ansariha F, Mirshafiey A. The Evaluation of Safety Property and Apoptotic Efficacy of α-L-Guluronic Acid (G2013), as a Novel NSAID, Under In Vitro Examination on L929 and Hepatocellular Carcinoma Cell Lines. Recent Advances in Inflammation & Allergy Drug Discovery. 2021;15(1):9-15.
Mahdian-Shakib A, Hashemzadeh MS, Anissian A, Oraei M, Mirshafiey A. Evaluation of the acute and 28-day sub-acute intravenous toxicity of α-l-guluronic acid (ALG; G2013) in mice. Drug and Chemical Toxicology. 2022;45(1):151-60.
Sharifi L, Aghamohammadi A, Mohsenzadegan M, Rezaei N, Towfighi Zavareh F, Moshiri M, et al. Immunomodulation of TLR2 and TLR4 by G2013 (alfa-L-Guluronic acid) in CVID Patients. International Journal of Pediatrics. 2017;5(7):5327-37.
Farhang H, Sharifi L, Dallal MMS, Moshiri M, Norouzbabaie Z, Bokaie S, et al. The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line. Current drug discovery technologies. 2019;16(1):91-5.
Hosseini F, Mahdian-Shakib A, Jadidi-Niaragh F, Enderami SE, Mohammadi H, Hemmatzadeh M, et al. Anti‐inflammatory and anti‐tumor effects of α-l-guluronic acid (G2013) on cancer-related inflammation in a murine breast cancer model. Biomedicine & Pharmacotherapy. 2018; 98:793-800.
Bagherian Z, Mirshafiey A, Mohsenzadegan M, Farajollahi MM. Evaluation of G2013 (α-L-guluronic acid) efficacy on PC-3 cells through inhibiting the expression of inflammatory factors. Clinical and experimental pharmacology & physiology. 2022;49(2):254-63.
Mortazavi-Jahromi SS, Alizadeh S, Javanbakht MH, Mirshafiey A. Anti-Diabetic and Angio-Protective Effect of Guluronic Acid (G2013) as a New Nonsteroidal Anti-Inflammatory Drug in the Experimental Model of Diabetes. Endocrine, metabolic & immune disorders drug targets. 2020;20(3):446-52.
Rehm B, Valla S. Bacterial alginates: biosynthesis and applications. Applied microbiology and biotechnology. 1997; 48:281-8.
Fattahi MJ, Abdollahi M, Agha Mohammadi A, Rastkari N, Khorasani R, Ahmadi H, et al. Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug. Immunopharmacology and immunotoxicology. 2015;37(6):535-40.
Sharifi L, Moshiri M, Dallal M, Asgardoon MH, Nourizadeh M, Bokaie S, et al. The Inhibitory Role of M2000 (β-D-Mannuronic Acid) on Expression of Toll-like Receptor 2 and 4 in HT29 Cell Line. Recent patents on inflammation & allergy drug discovery. 2019;13(1):57-65.
Mohsenzadegan M, Moghbeli F, Mirshafiey A, Farajollahi MM. Anti-tumor effect of M2000 (β-d-mannuronic acid) on the expression of inflammatory molecules in the prostate cancer cell. Immunopharmacology and Immunotoxicology. 2021;43(4):419-30.
Athari Nik Azm S, Vafa M, Sharifzadeh M, Safa M, Barati A, Mirshafiey A. Effects of M2000 (D-mannuronic acid) on learning, memory retrieval, and associated determinants in a rat model of Alzheimer’s disease. American Journal of Alzheimer's Disease & Other Dementias®. 2017;32(1):12-21. 273
Pourgholi F, Hajivalili M, Razavi R, Esmaeili S, Baradaran B, Movasaghpour AA, et al. The role of M2000 as an anti-inflammatory agent in toll-like receptor 2/microRNA-155 pathway. Avicenna journal of medical biotechnology. 2017;9(1):8.
Mortazavi-Jahromi SS, Alizadeh S, Javanbakht MH, Mirshafiey A. Anti-diabetic effect of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property on insulin production, blood glucose, and inflammatory markers in the experimental diabetes model. Archives of physiology and biochemistry. 2019;125(5):435-40.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Laleh Sharfi, Mohammad Reza Nowroozi, Galina Smirnova, Anna Fedotova, Dmitry Babarkin, Abbas Mirshafiey
This work is licensed under a Creative Commons Attribution 4.0 International License.
