• Suma Oommen Sen Gupta College of Technological Sciences, Ashram More, G.T. Road, Asansol 713301, West Bengal, India,
  • Amit Kumar Nayak Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj 757086, Odisha, India
  • Pritesh Devbhuti NSHM College of Pharmaceutical Technology, 124, B. L. Saha Road, Kolkata 700053, India,
  • Amitava Ghosh Bengal College of Pharmaceutical Sciences and Research, B.R.B. Sarani, Bidhannagar, Durgapur 713212, West Bengal, India


Scientists throughout the world are in search of novel modified biopolymer to fabricate smart drug delivery systems based on hydrogel formulations using several cross-linkers like glutaraldehyde, glyoxal, epichlorhydrin, adipic acid dihydrazide, carbodiimide, genipin, etc. Agents that are fused into the polymeric structure like isocyanates, glutaraldehyde, polyepoxides, etc., and are extremely toxic in nature. In addition, these are susceptible to percolate out into the body on biodegradation of polymeric structure. As an alternative to these toxic cross-linking agents, the periodate-Schiff base staining technique is widely being used for cross-linking in biology and biochemistry. The mechanism of this cross-linking technique is based on the reaction in-between the Schiff reagent and the aldehydes produced via the periodate oxidation. During past few decades, several researchers have already been studied on the natural gums and also, developed their dialdehyde derivatives via the periodate oxidation technique. These periodate oxidized gums are being used to cross-link gelatin, other proteins and chitosan to develop various smart systems for drug delivery, tissue engineering, wound dressing, edible films, etc. The current review presents a comprehensive discussion of the available reported literature on the periodate oxidation of various gums and their use as natural cross-linker.

Keywords: Dialdehyde gums, Periodate oxidation, Schiff reagent, Cross-linker


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Author Biography

Suma Oommen Sen, Gupta College of Technological Sciences, Ashram More, G.T. Road, Asansol 713301, West Bengal, India,

Asst.Professor in Pharmacy


1. Patel DP, Singh S. Chitosan: A multifacet polymer. Int J Curr Pharm Res 2015;7:21-8.
2. Vijayanand P, Deepa A, Bhagavan Raju M. Development, characterization and evaluation of soft oral edible gel using gellan gum. Int J Appl Pharm 2017;9:73-7.
3. Ahmed VA, Goli D. Development and characterization of in situ gel of xanthan for ophthalmic formulation containing brimonidine tartrate. Asian J Pharm Clin Res 2018;11:277-84.
4. Toppo FA, Pawar RS. Novel drug delivery strategies and approaches for wound healing managements. J Crit Rev 2015;2:12-20.
5. Reddy PS, Bose PSC, Sruthi V, Saritha D. Investigation of kondagogu to develop transdermal film of repaglinide. Asian J Pharm Clin Res 2018;11:440-5.
6. Hasnain MS, Nayak AK. Chitosan as responsive polymer for drug delivery applications, In: Makhlouf ASH, Abu-Thabit NY, (eds.,) Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications, Volume 1, Types and Triggers, Woodhead Publishing Series in Biomaterials, Elsevier Ltd., 2018: pp. 581-605.
7. Kim SH, Won CY, Chu CC. Synthesis and characterisation of dextran–maleic acid based hydrogel. J Biomed Mater Res 1999:46:160–70.
8. Nayak AK, Pal D. Plant-derived polymers: Ionically gelled sustained drug release systems, In: Mishra M, (ed.), Encyclopedia of Biomedical Polymers and Polymeric Biomaterials, Taylor & Francis Group, New York, NY 10017, U.S.A., Vol. VIII, 2016: pp 6002-17.
9. Pal D, Nayak AK. Alginates, blends and microspheres: Controlled drug delivery, In: Mishra M, (ed.), Encyclopedia of Biomedical Polymers and Polymeric Biomaterials, Taylor & Francis Group, New York, NY 10017, U.S.A., Vol. I, 2015: pp 89-98.
10. Guru PR, Bera H, Das M, Hasnain MS, Nayak AK. Aceclofenac-loaded Plantago ovata F. husk mucilage-Zn+2-pectinate controlled-release matrices. Starch - Stärke 2018;70: 1700136.
11. Jana S, Saha A, Nayak AK, Sen KK, Basu SK. Aceclofenac-loaded chitosan-tamarind seed polysaccharide interpenetrating polymeric network microparticles. Colloids Surf B: Biointerf 2013;105:303-9.
12. Bera H, Boddupalli S, Nayak AK. Mucoadhesive-floating zinc-pectinate-sterculia gum interpenetrating polymer network beads encapsulating ziprasidone HCl. Carbohydr Polym 2015;131:108-18.
13. Pal D, Nayak AK. Interpenetrating polymer networks (IPNs): Natural polymeric blends for drug delivery, In: Mishra M, (ed.), Encyclopedia of Biomedical Polymers and Polymeric Biomaterials, Taylor & Francis Group, New York, NY 10017, U.S.A., Vol. VI, 2015: pp 4120-4130.
14. Chen T, Embree HD, Brown EM, Taylor MM, Payne GF. Enzyme-catalyzed gel formation of gelatin and chitosan: potential for in situ applications. Biomater 2003;24:2831–41.
15. Lee KY, Mooney D. Hydrogels for tissue engineering. Chem Rev 2001;101:1869–79.
16. Kuijpers A, Engbers G, Krijgsveld J, Zaat SA, Dankert J, Feijen J. Crosslinking and characterization of gelatin matrices for biomedical applications. J Biomater Sci Polym 2000:11:225–43.
17. Speer D, Chavapil M, Eskelson C, Ulreich J. Biological effects of residual glutaraldehyde in glutaraldehyde-tanned collagen biomaterials. J Biomed Mater Res 1980:14:753–64.
18. Yogesh S, Ravikumar V, Anthony N, Douglas L. Applications of green chemistry in the manufacture of oligonucleotide drugs. Pure Appl Chem 2001:73:175–80.
19. Steven KM, John G, Chris D, Lisa N, David G, Alica W, et al. A green-by-design biocatalytic process for atorvastatin intermediate. Green Chem 2010;12:81-6.
20. Kristiansen KA, Potthast A, Christensen BE. Periodate oxidation of polysaccharides for modification of chemical and physical properties. Carbohydr Res 2010:345:1264–71.
21. Gomez CG, Rinaudo M, Villar MA. Oxidation of sodium alginate and characterization of the oxidized derivatives. Carbohydr Polym 2007;67:296–304.
22. Gupta B, Tummalapalli M, Deopura BL, Alam MS. Functionalization of pectin by periodate oxidation. Carbohydr Polym 2013:98:1160–5.
23. Guo J, Ge L, Li X, Mu C, Li D. Periodate oxidation of xanthan gum and its crosslinking effects on gelatin-based edible films. Food Hydrocol 2014:39:243-50.
24. Perlin AS. Glycol-cleavage oxidation. Adv Carbohydr Chem Biochem 2006:60:183–250.
25. Larsen B, Painter T. The periodate-oxidation limit of alginate. J Carbohydr Res 1969:10:186–7.
26. Malaprade L. Action of polyalcohols on periodic acid. Analytical application. Bull Soc Chim 1928:43:683–96.
27. Scott JE, Tigwell MJ. On the mechanism of scission of alginate chains by periodate. Carbohydr. Res. 1976:47105–117.
28. Painter T, Larsen B. Formation of hemiacetals between neighbouring hexuronic acid residues during periodate oxidation of alginate. Acta Chem. Scand. 1970:24:813–33.
29. Kang HA, Jeon GJ, Lee MY, Yang JW. Effectiveness test of alginate-derived polymeric surfactants. J Chem Technol Biotechnol 2002;77:205–10.
30. Liu M, Gao C, Chen J, Zhang X. Preparation and controlled degradation of oxidized sodium alginate hydrogel. Polym Degrad Stab 2009:94:1405–10.
31. Murali R, Thanikaivelan P, Cheirmadurai K, Collagen - poly(dialdehyde) guar gum based porous 3D scaffolds immobilized with growth factor for tissue engineering applications. Carbohydr Polym 2014: 114:399–406.
32. Wongsagon R, Shobsngob S, Varavinit S. Preparation and physicochemical properties of dialdehyde tapioca starch. Starch/Stärke 2005;57:166-72.
33. Li J, Hu W, Zhang Y, Tan H,Yan X, Zhao L, Liang H. pH and glucose dually responsive injectable hydrogel prepared by in situ crosslinking of phenylboronic modified chitosan and oxidized dextran. J Polym Sci Part A: Polym Chem 2015;53:1235–44.
34. Nayak AK, Bera H, Hasnain MS, Pal D. Graft-copolymerization of plant polysaccharides, In: V.K. Thakur (ed.,), Biopolymer Grafting, Synthesis and Properties, Elsevier Inc., 2018: pp. 1-62.
35. Jana S, Maji N, Nayak AK, Sen KK, Basu SK. Development of chitosan-based nanoparticles through inter-polymeric complexation for oral drug delivery. Carbohydr Polym 2013;98:870-6.
36. Jana S, Das A, Nayak AK, Sen KK, Basu SK. Aceclofenac-loaded unsaturated esterified alginate/gellan gum microspheres: In vitro and in vivo assessment. Int J Biol Macromol 2013;57:129-37.
37. Mu C, Guo J, Li X, Lin W, Li DF. Preparation and properties of dialdehyde carboxymethyl cellulose crosslinked gelatin edible films. Food Hydrocol 2012;27:22-9.
38. Balakrishnan B, Jayakrishnan A. Self-cross-linking biopolymers as injectable in situ forming biodegradable scaffolds. Biomater 2005:26: 3941–51.
39. Dash R, Foston M, Ragauskas A. Improving the mechanical and thermal properties of gelatin hydrogels cross-linked by cellulose nanowhiskers, Carbohydr Polym 2013:91:638–45.
40. Draye JP, Delaey, Voorde AV, Bulcke AV, Bogdanov B, Schacht E. In-vitro release characteristics of bioactive molecules from dextran dialdehyde cross-linked gelatin hydrogel films. Biomater 1998;19:99–107.
41. Bouhadir K, Lee K, Alsberg E, Damm K, Anderson K, Mooney D. Degradation of partially oxidized alginate and its potential application for tissue engineering. Biotechnol Prog 2001;17: 945–50.
42. Yu X, Xu Y, Li L, Gua Z, Zhang X. Feasibility study of a novel crosslinking reagent (alginate dialdehyde) for biological tissue fixation. Carbohydr Polym 2012;87:1589–95.
43. Wan C, Chen F, Tian M, Zhang D, Wang J, Wang Q, et al. Preparation and characterization of oxidized alginate covalently cross-linked galactosylated chitosan scaffold for liver tissue engineering. Mater Sci Eng C. 2012: 32: 310–320.
44. Matricardi P, Pescosolidoa L, Piroa T, Vermondenb T, Covielloa T, Alhaiquea F, Hennink WE. Biodegradable IPNs based on oxidized alginate and dextran-HEMA for controlled release of proteins. Carbohydr Polym 2011;86:208–13.
45. Jayakrishnan A, Balakrishnan B, Mohanty M, Umashankar PR. Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatine. Biomater 2005;26:6335–42.
46. Bigi A, Boanini E, Rubini K, Panzavolta S. Chemico-physical characterization of gelatin films modified with oxidized alginate. Acta Biomater 2010;6:383–8.
47. Guo J, Li X, Mu C, Zhang H, Qin P, Li D. Freezing -thawing effects on the properties of dialdehyde carboxymethyl cellulose crosslinked gelatin-MMT composite films. Food Hydrocol. 2013;33:273-9.
48. Serrero A, Trombotto S, Cassagnau P, Bayon Y, Gravagna P, Montanari S, et al. Polysaccharide gels based on chitosan and modified starch: Structural characterization and linear viscoelastic behavior. Biomacromol 2010;11:1534–43.
49. Hua Y, Liua L, Gu Z, Dana W, Dana N, Yu X. Modification of collagen with a natural derived cross-linker, alginate dialdehyde. Carbohydr Polym 2014;102:324-32.
50. Xu Y, Huang C, Li L, Yu X, Wang X, Peng H, et al. In vitro enzymatic degradation of a biological tissue fixed by alginate dialdehyde. Carbohydr Polym 2013:95:148– 54.
51. Sarika PR, Cinthya K, Jayakrishnan A, Anilkumar PR, James NR. Modified gum arabic cross-linked gelatin scaffold for biomedical applications. Mater Sci Eng C Mater Biol Appl 2014;43:272-9.
52. Sarika PR and James NR. Preparation and characterisation of gelatin-gum arabic aldehyde nanogels via inverse miniemulsion technique. Int J Biol Macromol 2015;76:181-7.
53. Balakrishnan B, Soman D, Payanam U, Laurent A, Labarre D, Jayakrishnan A. A novel injectable tissue adhesive based on oxidized dextran and chitosan: Acta Biomater 2017;53:343-54.
54. Hu J, Quan Y, Lai Y, Zheng Z, Hu Z, Wang X, et al. A smart aminoglycoside hydrogel with tunable gel degradation, on-demand drug release, and high antibacterial activity. J Control Release 2017;247:145–52.
55. Li S, Wang J, Song L, Zhou Y, Zhao J, Hou X, Yuan X,. Injectable PAMAM/ODex double-crosslinked hydrogels with high mechanical strength. Biomed Mater 2016;12:015012.
56. Serrero A, Trombotto S, Cassagnau P, Bayon Y, Gravagna P, Montanari S, et al. Polysaccharide gels based on chitosan and modified starch: Structural characterization and linear viscoelastic behavior. Biomacromol 2010;11:1534–43.
57. Karvinen J, Koivisto JT, Jönkkäri I, Kellomäki M. The production of injectable hydrazone crosslinked gellan gum-hyaluronan hydrogels with tunable mechanical and physical properties. J Mech Behav Biomed Mater 2017;71:383–91.
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How to Cite
Sen, S. O., A. K. Nayak, P. Devbhuti, and A. Ghosh. “MODIFICATION OF GUMS BY PERIODATE OXIDATION: A NATURAL CROSS-LINKER”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 11, no. 7, May 2019,
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