Chemical Modifications of Alginates for Biomedical Applications-A Review

  • Muhammad Naqeeb Ur Rehman Qureshi Department of Zoology and Biology, Faculty of Sciences, Pir Mehr Ali Shah ARID Agriculture University Rawalpindi, Pakistan.
  • Atta Rasool School of Chemistry, University of the Punjab, Lahore, Pakistan.
  • Muhammad Anees Ur Rehman Qureshi Department of Chemistry, Allama Iqbal Open University, Islamabad.
  • Muhammad Jahanzaib Javaid Al-Wedad General Medical Group, Al-Wesam, Al-taif, Makkah Region, Saudi Arabia
  • Maria Kanwal Department of Bioinformatics and Biosciences, CUST, Islamabad.
  • Muhammad Asad Anwar Department of Bioinformatics and Biosciences, CUST, Islamabad.
  • Muhammad Shoaib Butt School of Chemical and Materials Engineering (SCME) National University of Science and Technology, 44000 Islamabad, Pakistan.
  • Naila Firdous Department of Chemistry, University of Kotli, Azad Kashmir, Pakistan.
Keywords: alginate (Alg), bioavailability, biomedical applications, modified alginate

Abstract

Abstract Views: 0

In current pharmaceutical developments biopolymers have earned a unique position as a choice of excipient not only by affecting formulation developments but also imparting biocompatibility, degradability and stimuli responsiveness for controlled drug release in living systems. Alginate (Alg) is a versatile, flexible, bioactive, non-toxic and inexpensive biopolymers obtained from brown seaweeds and some exo-polysaccharide producing bacteria. Native Alg is susceptible to faster degradation, dimensional instability, de-polymerization at high temperature and low pH precipitation. Therefore, its chemical modifications attracted researcher in order to improve biological, chemical and physicochemical properties by tailoring its hydroxyl and carboxylic functional groups via oxidation, reductive amination, acetylation, phosphorylation, sulfation, esterification, amidation and Ugi reactions.  These modifications are carried out by blending, cross-linking and grafting to enable the use of Alg to improve cell affinity, gelation, mechanical strength, structural, functional flexibility and encapsulation for drug delivery, wound healing, tissue engineering, cancer treatments, food packaging, metal adsorption, wastewater treatment and cosmetics. The active sites in the Alg are generated by the use of initiator, cross-linker or irradiation. In this review, sources, properties and different chemical reactions used for making alginate derivatives are summarized. In the end, applications of modified Alg in medico-biological, environmental and food industry are briefly stated.

Downloads

Download data is not yet available.

References

Rasool A, Islam A, Fayyaz S. Hydrogels and their emerging applications. In: Kumar A, Gupta R, eds. Hydrogels: Fundamentals to Advanced Energy Applications. CRC Press; 2023:103-126.

Reig-Vano B, Tylkowski B, Montané X, Giamberini M. Alginate-based hydrogels for cancer therapy and research. Int J Biol Macromol. 2021;170:424-436. https://doi.org/10.1016/j.ijbiomac.2020.12.161

Ata S, Rasool A, Islam A, Bibi I, Iqbal M. Loading of cefixime to pH sensitive chitosan based hydrogel and investigation of controlled release kinetics. Int J Biol Macromol. 2020;155:1236-1244. https://doi.org/10.1016/j.ijbiomac.2019.11.091

Qureshi MAUR, Arshad N, Rasool A, Rizwan M, Fawy KF, Rasheed T. pH-responsive chitosan dendrimer hydrogels enabling controlled cefixime release. Eur Polym J. 2024;219:e113377. https://doi.org/10.1016/j.eurpolymj.2024.113377

Arshad N, Chaudhary AA, Saleem S, Akram M, Qureshi MAUR. Surface modification of surgical suture by chitosan-based biocompatible hybrid coatings: in-vitro anti-corrosion, antibacterial, and in-vivo wound healing studies. Int J Biol Macromol. 2024;281:e136571. https://doi.org/10.1016/j.ijbiomac.2024.136571

Azeem MK, Islam A, Rizwan M, Gul N, RU Khan, Raseed T. Sustainable and environment friendlier carrageenan-based pH-responsive hydrogels: Swelling behavior and controlled release of fertilizers. Colloid Polym Sci. 2023;301(3):209-219. https://doi.org/10.1007/s00396-023-05054-9

Naz M, Jabeen S, Gull N, et al. Novel silane crosslinked chitosan based electrospun nanofiber for controlled release of benzocaine. Front Mater. 2022;9:e826251. https://doi.org/10.3389/fmats.2022.826251

Azeem MK, Rizwan M, Islam A, et al. In-house fabrication of macro-porous biopolymeric hydrogel and its deployment for adsorptive remediation of lead and cadmium from water matrices. Environ Res. 2022;214:e113790. https://doi.org/10.1016/j.envres.2022.113790

Rasool A, Ata S, Islam A, Khan RU. Fabrication of novel carrageenan based stimuli responsive injectable hydrogels for controlled release of cephradine. RSC Adv. 2019;9(22):12282-12290. https://doi.org/10.1039/C9RA02130B

Naz M, Rizwan M, Jabeen S, et al. Cephradine drug release using electrospun chitosan nanofibers incorporated with halloysite nanoclay. Z Physe Chem. 2022;236(2):227-238. https://doi.org/10.1515/zpch-2021-3072

Gomez CG, Rinaudo M, Villar MA. Oxidation of sodium alginate and characterization of the oxidized derivatives. Carbohydr Polym. 2007;67(3):296-304. https://doi.org/10.1016/j.carbpol.2006.05.025

Kang H-A, Shin MS, Yang J-W. Preparation and characterization of hydrophobically modified alginate. Polym Bull. 2002;47(5):429-435. https://doi.org/10.1007/s002890200005

Rizwan M, Selvanathan V, Rasool A, Iqbal DN, Kanwal Q, Shafqat SS, Bilal M. Metal–organic framework-based composites for the detection and monitoring of pharmaceutical compounds in biological and environmental matrices. Water Air Soil Pollut. 2022;233(12):e493. https://doi.org/10.1007/s11270-022-05904-2

Li Z, Ni C, Xiong C, Li Q. Preparation and drug release of hydrophobically modified alginate. Chem. 2009;1:93-96.

Alban S, Schauerte A, Franz G. Anticoagulant sulfated polysaccharides: part I. Synthesis and structure–activity relationships of new pullulan sulfates. Carbohydr Polym. 2002;47(3):267-276. https://doi.org/10.1016/S0144-8617(01)00178-3

Xue Y-T, Li S, Liu W-J, Xin M, Li HH, Yu GL. The mechanisms of sulfated polysaccharide drug of propylene glycol alginate sodium sulfate (PSS) on bleeding side effect. Carbohydr Polym. 2018;194:365-374. https://doi.org/10.1016/j.carbpol.2018.04.048

Pawar SN. Chemical modification of alginate. In: Venkatesan J, Anil S, Kim S-K, eds. Seaweed polysaccharides: isolation, Biological and Biomedical Applications. Elsevier; 2017:111-155.

Sand A, Yadav M, Behari K. Synthesis and characterization of alginate‐g‐vinyl sulfonic acid with a potassium peroxydiphosphate/thiourea system. J App Polym Sci. 2010;118(6):3685-3694. https://doi.org/10.1002/app.32447

Rasool A, Hafeez S, Islam A, et al. Polymer nanocomposite films and coatings for biomedical applications. In: Pandey M, Deshmukh K, Hussain CM, eds. Polym Nanocompos Films and Coatings: Processes, Fundamental Properties and Applications. Elsevier; 2024:729-758.

Sen G, Singh RP, Pal S. Microwave‐initiated synthesis of polyacrylamide grafted sodium alginate: synthesis and characterization. J App Polym Sci. 2010;115(1):63-71. https://doi.org/10.1002/app.30596

Arshad N, Rasool A. Graphene oxide reinforced biopolymeric (chitosan) hydrogels for controlled cephradine release. Int J Biol Macromol. 2023;242:e124948. https://doi.org/10.1016/j.ijbiomac.2023.124948

Azeem MK, Islam A, Khan RU, Sher F, Rasheed T. Eco‐friendly three‐dimensional hydrogels for sustainable agricultural applications: current and future scenarios. Polym Adv Technol. 2023;34(9):3046-3062. https://doi.org/10.1002/pat.6122

Rasool A, Ata S, Islam A. Stimuli responsive biopolymer (chitosan) based blend hydrogels for wound healing application. Carbohydr Polym. 2019;203:423-429. https://doi.org/10.1016/j.carbpol.2018.09.083

Pluemsab W, Sakairi N, Furuike T. Synthesis and inclusion property of α-cyclodextrin-linked alginate. Polym. 2005;46(23):9778-9783. https://doi.org/10.1016/j.polymer.2005.08.005

Huamani-Palomino RG, Córdova BM, Pichilingue LER, Venâncio T, Valderrama AC. Functionalization of an alginate-based material by oxidation and reductive amination. Polym. 2021;13(2):e255. https://doi.org/10.3390/polym13020255

Yao Z-a, Xu L, Wang B-x, Ye T-t, Li Y-f, Wu H-g. Optimization of preparation conditions, molecular structure analysis and antitumor activity of sulfated sodium alginate oligosaccharides. Eur Polym J. 2023;201:e112571. https://doi.org/10.1016/j.eurpolymj.2023.112571

Li Q-Q, Xu D, Dong Q-W, Song X-J, Chen Y-B, Cui Y-L. Biomedical potentials of alginate via physical, chemical, and biological modifications. Int J Biol Macromol. 2024;277:e134409. https://doi.org/10.1016/j.ijbiomac.2024.134409

Azad AK, Sulaiman WMAW, Almoustafa H, Dayoob M, Kumarasamy V, Subramaniyan V. A dataset of microstructure features of electro-hydrodynamic assisted 5-fluorouracil-grafted alginate microbeads and physicochemical properties for effective colon targeted carriers drug delivery. Data Brief. 2024;53:e110202. https://doi.org/10.1016/j.dib.2024.110202

Sadeghi M, Habibi Y, Bohlool T, Mohamadnia Z, Nikfarjam N, Norouzi M. Fabrication of a self-healing hydrogel with antibacterial activity using host-guest interactions between dopamine-modified alginate and β-cyclodextrin dimer. Int J Biol Macromol. 2024;273:e132827. https://doi.org/10.1016/j.ijbiomac.2024.132827

Román-Guerrero A, Cortés-Camargo S, Alpizar-Reyes E. Chemically modified alginate-based hydrogel-matrices in drug delivery. Macromol. 2025;5(3):e36. https://doi.org/10.3390/macromol5030036

Zhang H, Zhou L, Shehzad H, et al. Innovative free radical induced synthesis of WO3-doped diethyl Malonate grafted chitosan encapsulated with phosphorylated alginate matrix for UO22+ adsorption: parameters optimisation through response surface methodology. Sep Purif Technol. 2025;353:e128455. https://doi.org/10.1016/j.seppur.2024.128455

Chen X, Zhu Q, Liu C, Li D, Yan H, Lin Q. Esterification of alginate with alkyl bromides of different carbon chain lengths via the bimolecular nucleophilic substitution reaction: synthesis, characterization, and controlled release performance. Polym. 2021;13(19):e3351. https://doi.org/10.3390/polym13193351

Zongrui T, Yu C, Wei L. Grafting derivate from alginate. In: Thakur VK, ed. Biopolym Graftin: Synthesis and Properties. Elsevier; 2018:115-173.

Yang L, Zhang B, Wen L, Liang Q, Zhang L-M. Amphiphilic cholesteryl grafted sodium alginate derivative: synthesis and self-assembly in aqueous solution. Carbohydr Polym. 2007;68(2):218-225. https://doi.org/10.1016/j.carbpol.2006.12.020

Broderick E, Lyons H, Pembroke T, Byrne H, Murray B, Hall M. The characterisation of a novel, covalently modified, amphiphilic alginate derivative, which retains gelling and non-toxic properties. J Colloid Interface Sci. 2006;298(1):154-161. https://doi.org/10.1016/j.jcis.2005.12.026

Pawar SN, Edgar KJ. Alginate esters via chemoselective carboxyl group modification. Carbohydr Polym. 2013;98(2):1288-1296. https://doi.org/10.1016/j.carbpol.2013.08.014

Chhatbar MU, Prasad K, Chejara DR, Siddhanta A. Synthesis of sodium alginate based sprayable new soft gel system. Soft Matt. 2012;8(6):1837-1844. https://doi.org/10.1039/C2SM06947D

Taubner T, Marounek M, Synytsya A. Preparation and characterization of amidated derivatives of alginic acid. Int J Biol Macromol. 2017;103:202-207. https://doi.org/10.1016/j.ijbiomac.2017.05.070

Abulateefeh SR, Khanfar MA, Al Bakain RZ, Taha MO. Synthesis and characterization of new derivatives of alginic acid and evaluation of their iron (III)-crosslinked beads as potential controlled release matrices. Pharm Dev Technol. 2014;19(7):856-867. https://doi.org/10.3109/10837450.2013.836222

Bu H, Kjøniksen A-L, Elgsaeter A, Nyström B. Interaction of unmodified and hydrophobically modified alginate with sodium dodecyl sulfate in dilute aqueous solution: Calorimetric, rheological, and turbidity studies. C Colloids and Surf: Physicochem Eng Asp. 2006;278(1-3):166-174. https://doi.org/10.1016/j.colsurfa.2005.12.016

Tang Y, Chen K, Li J, Feng Y, Yu G, Wang L. Electrolyte and pH-sensitive amphiphilic alginate: synthesis, self-assembly and controlled release of acetamiprid. RSC Adv. 2018;8(56):32193-32199. https://doi.org/10.1039/C8RA05503C

Chen S, Li C, Teng Y, Wei H, Lu C, Yang H. Photothermal and antimicrobial properties of catechol-chitosan silver nanoparticles/esterified sodium alginate composite hydrogels. J Biomater Sci Polym Ed. 2025:1-20. https://doi.org/10.1080/09205063.2025.2526292

Qiu L, Shen R, Wei L, et al. Designing a microbial fermentation-functionalized alginate microsphere for targeted release of 5-ASA using nano dietary fiber carrier for inflammatory bowel disease treatment. J Nanobiotechnol. 2023;21(1):e344. https://doi.org/10.1186/s12951-023-02097-6

Bu Y, Chen X, Wu T, Zhang R, Yan H, Lin Q. Synthesis, optimization and molecular self-assembly behavior of alginate-g-oleylamine derivatives based on ugi reaction for hydrophobic drug delivery. Int J Mol Sci. 2024;25(15):e8551. https://doi.org/10.3390/ijms25158551

Shahroz M, Arshad N. Investigating synergistic effects of biomass-derived carbon coatings on TiO2 for anode candidacy in electrochemical OER and supercapacitor performance enhancement. Int J Hydrogen Energy. 2025;137:214-224. https://doi.org/10.1016/j.ijhydene.2025.05.117

Freitas ED, Vidart JM, Silva EA, da Silva MG, Vieira MG. Development of mucoadhesive sericin/alginate particles loaded with ibuprofen for sustained drug delivery. Particuol. 2018;41:65-73. https://doi.org/10.1016/j.partic.2017.12.011

Rasool A, Ata S, Islam A, Mehmood A, Khan RU, Mahmood HA. Kinetics and controlled release of lidocaine from novel carrageenan and alginate-based blend hydrogels. Int J Biol Macromol. 2020;147:67-78. https://doi.org/10.1016/j.ijbiomac.2020.01.073

Rasool A, Rizwan M, Rasheed T, Bilal M. Thermo-responsive functionalized polymeric nanocomposites. In: Ali N, Bilal M, Khan A, Nguyen TA, Gupta RK, eds. Smart Polym Nanocompos: Design, Synthesis, Functionalization, Properties, and Applications. Elsevier; 2023:219-240.

Banks SR, Enck K, Wright M, Opara EC, Welker ME. Chemical modification of alginate for controlled oral drug delivery. J Agricult Food Chem. 2019;67(37):10481-10488. https://doi.org/10.1021/acs.jafc.9b01911

Thomas D, Mathew N, Nath MS. Starch modified alginate nanoparticles for drug delivery application. Int J Biol Macromol. 2021;173:277-284. https://doi.org/10.1016/j.ijbiomac.2020.12.227

Gao B, Chen L, Zhao Y, et al. Methods to prepare dopamine/polydopamine modified alginate hydrogels and their special improved properties for drug delivery. Eur Polym J. 2019;110:192-201. https://doi.org/10.1016/j.eurpolymj.2018.11.025

Liu W, Zhai Y, Heng X, et al. Oral bioavailability of curcumin: problems and advancements. J Drug Target. 2016;24(8):694-702. https://doi.org/10.3109/1061186X.2016.1157883

Boi S, Rouatbi N, Dellacasa E, Di Lisa D, Bianchini P, Monticelli O. Alginate microbeads with internal microvoids for the sustained release of drugs. Int J Biol Macromol. 2020;156:454-461. https://doi.org/10.1016/j.ijbiomac.2020.04.083

Yun Y, Wu H, Gao J, et al. Facile synthesis of Ca2+-crosslinked sodium alginate/graphene oxide hybrids as electro-and pH-responsive drug carrier. Mater Sci Eng: C. 2020;108:e110380. https://doi.org/10.1016/j.msec.2019.110380

Qureshi MAUR, Arshad N, Rasool A, Janjua NK, Butt MS, Ismail H. Kappa-carrageenan and sodium alginate-based pH-responsive hydrogels for controlled release of methotrexate. R Soc Open Sci. 2024:e231952. https://doi.org/10.1098/rsos.231952

Aycan D, Gül İ, Yorulmaz V, Alemdar N. Gelatin microsphere-alginate hydrogel combined system for sustained and gastric targeted delivery of 5-fluorouracil. Int J Biol Macromol. 2024;255:e128022. https://doi.org/10.1016/j.ijbiomac.2023.128022

Sorasitthiyanukarn FN, Muangnoi C, Bhuket PRN, Rojsitthisak P, Rojsitthisak P. Chitosan/alginate nanoparticles as a promising approach for oral delivery of curcumin diglutaric acid for cancer treatment. Mater Sci Eng: C. 2018;93:178-190. https://doi.org/10.1016/j.msec.2018.07.069

Mor N, Raghav N. In-vitro simulation of modified-alginate ester as sustained release delivery system for curcumin. J Mol Str. 2023;1283:e135307. https://doi.org/10.1016/j.molstruc.2023.135307

Cao B, Wang C, Guo P, et al. Photo-crosslinked enhanced double-network hydrogels based on modified gelatin and oxidized sodium alginate for diabetic wound healing. Int J Biol Macromol. 2023;245:e125528. https://doi.org/10.1016/j.ijbiomac.2023.125528

Bautista GFM, Vidallon MLP, Salamanez KC, Rodriguez EB. Nanodelivery system based on zein-alginate complexes enhances in vitro chemopreventive activity and bioavailability of pomelo seed limonoids. J Drug Deliv Sci Technol. 2019;54:e101296. https://doi.org/10.1016/j.jddst.2019.101296

Wang Y, Liu M, Ni B, Xie L. κ-Carrageenan–sodium alginate beads and superabsorbent coated nitrogen fertilizer with slow-release, water-retention, and anticompaction properties. Indust Eng Chem Res. 2012;51(3):1413-1422. https://doi.org/10.1021/ie2020526

Kirdponpattara S, Khamkeaw A, Sanchavanakit N, Pavasant P, Phisalaphong M. Structural modification and characterization of bacterial cellulose–alginate composite scaffolds for tissue engineering. Carbohydr Polym. 2015;132:146-155. https://doi.org/10.1016/j.carbpol.2015.06.059

Eltabeeb MA, Hamed RR, El-Nabarawi MA, et al. Nanocomposite alginate hydrogel loaded with propranolol hydrochloride kolliphor® based cerosomes as a repurposed platform for methicillin-resistant Staphylococcus aureus-(MRSA)-induced skin infection; in-vitro, ex-vivo, in-silico, and in-vivo evaluation. Drug Deliv Transl Res. 15, 556–576. https://doi.org/10.1007/s13346-024-01611-z

Zhu H, Tong AH, Fu Y, Chen Z, Jin Z, Guo S. Optimizing alginate dressings with allantoin and chemical modifiers to promote wound healing. Int J Biol Macromol. 2024;275:e133524. https://doi.org/10.1016/j.ijbiomac.2024.133524

Sikach A, Konovalova V, Kolesnyk I. Hydrogel films based on sodium alginate modified with octane-1-amine: enhanced pore formation and potential applications in drug delivery systems. Chem Phys Technol Surf. 2024;15(1):43-56

Mofazali P, Atapour M, Nakamura M, Sheikholeslam M, Galati M, Saboori A. Surface modification of additive manufactured Ti6Al4V scaffolds with gelatin/alginate- IGF-1 carrier: an effective approach for healing bone defects. Int J Biol Macromol. 2024;265:e131125. https://doi.org/10.1016/j.ijbiomac.2024.131125

Arslan AK, Aydoğdu A, Tolunay T, Basat Ç, Bircan R, Demirbilek M. The effect of alginate scaffolds on bone healing in defects formed with drilling model in rat femur diaphysis. J Biomed Mater Res B: App Biomater. 2023;111(6):1299-1308. https://doi.org/10.1002/jbm.b.35233

Zhang Q, Li J, Qu Q, Pan S, Yu K, Liu Y. Graphene oxide modified sodium alginate/polyethylene glycol phase change material hydrogel scaffold composite with photothermal temperature control for potential bone tissue regeneration. J Mater Res Technol. 2024;30:2446-2457. https://doi.org/10.1016/j.jmrt.2024.04.009

Zhao W, Bai B, Hong Z, Zhang X, Zhou B. Berbamine (BBM), a natural STAT3 inhibitor, synergistically enhances the antigrowth and proapoptotic effects of sorafenib on hepatocellular carcinoma cells. ACS Omega. 2020;5(38):24838-24847. https://doi.org/10.1021/acsomega.0c03527

Shen Y, Wang H, Li W, et al. Synthesis and characterization of double-network hydrogels based on sodium alginate and halloysite for slow release fertilizers. Int J Biol Macromol. 2020;164:557-565. https://doi.org/10.1016/j.ijbiomac.2020.07.154

Azeem MK, Islam A, Khan RU, Shuib RK, Rehman A, Sadiqa A. Guar gum/poly ethylene glycol/graphene oxide environmentally friendly hybrid hydrogels for controlled release of boron micronutrient. R Soc Open Sci. 2023;10(12):e231157. https://doi.org/10.1098/rsos.231157

Yan P, Lan W, Xie J. Modification on sodium alginate for food preservation: a review. Trends Food Sci Technol. 2024;143:e104217. https://doi.org/10.1016/j.tifs.2023.104217

Farooq U, Athar M, Salman M, Rehmat N. Biosorptive removal of Pb (II) and Cd (II) ions from aqueous solution by dried biomass from Ficus religiosa. Desal Water Treat. 2017;82:201-209. https://doi.org/10.5004/dwt.2017.21008

Benettayeb A, Guibal E, Morsli A, Kessas R. Chemical modification of alginate for enhanced sorption of Cd (II), Cu (II) and Pb (II). Chem Eng J. 2017;316:704-714. https://doi.org/10.1016/j.cej.2017.01.131

Abd-Elhamid A, Elgoud EA, Aly H. Alginate modified graphene oxide for rapid and effective sorption of some heavy metal ions from an aqueous solution. Cellulose. 2022;29(11):6231-6245. https://doi.org/10.1007/s10570-022-04656-w

Zhang H, Han X, Liu J, et al. Fabrication of modified alginate-based biocomposite hydrogel microspheres for efficient removal of heavy metal ions from water. Colloids and Surf: Physicochem Eng Asp. 2022;651:e129736. https://doi.org/10.1016/j.colsurfa.2022.129736

Published
2025-10-15
How to Cite
1.
Muhammad Naqeeb Ur Rehman Qureshi, Rasool A, Muhammad Anees Ur Rehman Qureshi, Javaid MJ, Maria Kanwal, Muhammad Asad Anwar, Muhammad Shoaib Butt, Naila Firdous. Chemical Modifications of Alginates for Biomedical Applications-A Review. Sci Inquiry Rev [Internet]. 2025Oct.15 [cited 2025Nov.15];9(2):37-6. Available from: https://journals.umt.edu.pk/index.php/SIR/article/view/7457
Section
Chemistry