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Volume 22, Issue 1
  • ISSN: 1570-1794
  • E-ISSN: 1875-6271

Abstract

Aims

The aims of this study are to synthesize new derivatives of sodium alginate that improve the inherent properties, such as hydrogel strengthening, and create environmental sensitivity, such as pH sensitivity, for use in drug delivery.

Introduction

Today, hydrogels, due to outstanding properties such as biodegradability, biocompatibility, mechanical properties, and response to stimuli properties, are widely used as harmless biomaterials in various fields in drug delivery, wound dressing, and tissue engineering. Stimulus-sensitive polymers significantly respond to slight changes in their environment. Different types of stimuli are used to influence the properties of polymers, the most important of which are temperature and pH because these are two vital factors in the human body; hence, temperature-sensitive and pH-sensitive hydrogels have been extensively studied. The ability to absorb water and swell the hydrogel is due to hydrophilic chains in the hydrogel network, and water absorption by hydrogel can be controlled by response to the stimuli. Since hydrogels mimic human tissue, the ability to retain water in them is essential. As a result, it is considered in many biomedical drug delivery systems. Stimulus-responsive swelling can control diffusion out of and into the hydrogel network, which allows temporal and spatial control of drug release. When a drug is loaded onto a biodegradable and stimuli-sensitive hydrogel, the drug delivery system has the added advantage of sustained release of the drug, which reduces side effects.

Methods

In this study, two different hydrocarbons, [1,3-diaminopropane (DAP)] as a short-chain hydrocarbon, and [1,7-diaminoheptane (DAH)] as a long-chain hydrocarbon were grafted onto three types of sodium alginate (SA), through amide bond linkages. The hydrogel copolymer matrices were compared with sodium alginate (SA) beads. The graft copolymers were characterized using FTIR, 1HNMR, XRD spectroscopy, elemental analysis (CHNS) and thermal analysis (TGA, DTA and DSC). An environmental scanning electron microscope (ESEM) was used to investigate the surface morphology of hydrogels.

Results

Effects of variables such as the length of hydrocarbon chains cross-linked to alginate, temperature, pH, and cross-linkers on the properties of hydrogels investigated in the temperature range of 2-70˚C and two different pH values (4.4 and 7.4). The results showed that when the hydrocarbon chain length of diamines decreases, the extent of cross-linking and strength of the hydrogels are increased. Other results suggest that the hydrogels obtained from high-viscosity alginate derivatives had positive pH sensitivity. Hydrogels prepared in this study demonstrated good mechanical and swelling ratios that are necessary for wound dressing.

Conclusion

DAP-g-SA and DAH-g-SA pH-sensitive hydrogels were successfully synthesized through amide bond linkages. The new synthesis derivatives showed lower swelling levels at low pH (4.4). In contrast, their swelling levels at higher pH (7.4) were significantly enhanced. Higher swelling degree could be obtained at high pH. pH-responsive hydrogels are especially useful for various biological applications due to their unique feature of controlled swelling, biodegradability, biocompatibility, and fluid retention in their network structures. pH-responsive hydrogels, as intelligent systems, can be used in controlled-release drug delivery systems such as insulin delivery.

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2023-11-03
2025-06-24

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References

  1. AhmedE.M. Hydrogel: Preparation, characterization, and applications: A review.J. Adv. Res.20156210512110.1016/j.jare.2013.07.006 25750745
     [Google Scholar]
  2. HoffmanA.S. Hydrogels for biomedical applications.Adv. Drug Deliv. Rev.200254131210.1016/S0169‑409X(01)00239‑3 11755703
     [Google Scholar]
  3. ChatterjeeS. Stimuli-responsive hydrogels: An interdisciplinary overview.Hydrogels; IntechOpen2019
     [Google Scholar]
  4. OzdilD. WimpennyI. AydinH.M. YangY. Science and principles of biodegradable and bioresorbable medical polymers. In: 13 - Biocompatibility of biodegradable medical polymers; Xiang, Z.Woodhead Publishing2017379414
     [Google Scholar]
  5. Ahmad RausR. Wan NawawiW.M.F. NasaruddinR.R. NasaruddinR.R. Alginate and alginate composites for biomedical applications.Asian Journal of Pharmaceutical Sciences202116328030610.1016/j.ajps.2020.10.001 34276819
     [Google Scholar]
  6. LeeH. PietrasikJ. SheikoS.S. MatyjaszewskiK. Stimuli-responsive molecular brushes.Prog. Polym. Sci.2010351-2244410.1016/j.progpolymsci.2009.11.002
     [Google Scholar]
  7. SongJ. YuR. WangL. ZhengS. LiX. Poly(N-vinylpyrrolidone)-grafted poly(Nisopropylacrylamide) copolymers: Synthesis, characterization and rapid deswelling and reswelling behavior of hydrogels.Polymer 201152919831997
     [Google Scholar]
  8. WangF.Q. LiP. ZhangJ.P. WangA.Q. WeiQ. pH-sensitive magnetic alginate-chitosan beads for albendazole delivery.Pharm. Dev. Technol.201116322823610.3109/10837451003592217 20136349
     [Google Scholar]
  9. KimuraK. SakamotoH. NakamuraT. Application of photoresponsive polymers carrying crown ether and spirobenzopyran side chains to photochemical valve.J. Nanosci. Nanotechnol.2006661741174910.1166/jnn.2006.232 17025078
     [Google Scholar]
  10. HuangR. KostanskiL.K. FilipeC.D.M. GhoshR. Environment-responsive hydrogel-based ultrafiltration membranes for protein bioseparation.J. Membr. Sci.20093361-2424910.1016/j.memsci.2009.03.002
     [Google Scholar]
  11. ChenH. PalmeseG.R. ElabdY.A. Electrosensitive permeability of membranes with oriented polyelectrolyte nanodomains.Macromolecules200740478178210.1021/ma062678q
     [Google Scholar]
  12. YangW.C. XieR. PangX.Q. JuX-J. ChuL-Y. Preparation and characterization of dual stimuli-responsive microcapsules with a superparamagnetic porous membrane and thermo-responsive gates.J. Membr. Sci.2008321232433010.1016/j.memsci.2008.05.016
     [Google Scholar]
  13. Ramesh BabuV. Krishna RaoK.S.V. SairamM. NaiduB.V.K. HosamaniK.M. AminabhaviT.M. pH sensitive interpenetrating network microgels of sodium alginate-acrylic acid for the controlled release of ibuprofen.J. Appl. Polym. Sci.20069952671267810.1002/app.22760
     [Google Scholar]
  14. ChanG. MooneyD.J. New materials for tissue engineering: Towards greater control over the biological response.Trends Biotechnol.200826738239210.1016/j.tibtech.2008.03.011 18501452
     [Google Scholar]
  15. HoffmannJ. Plötner, M.; Kuckling, D.; Fischer, W.J. Photopatterning of thermally sensitive hydrogels useful for microactuators.Sens. Actuators A Phys.199977213914410.1016/S0924‑4247(99)00080‑1
     [Google Scholar]
  16. DonT.M. ChenH.R. Synthesis and characterization of AB-crosslinked graft copolymers based on maleilated chitosan and N-isopropylacrylamide.Carbohydr. Polym.200561333434710.1016/j.carbpol.2005.05.025
     [Google Scholar]
  17. IşıklanN. KüçükbalcıG. Microwave-induced synthesis of alginate-graft-poly(N-isopropylacrylamide) and drug release properties of dual pH- and temperature-responsive beads.Eur. J. Pharm. Biopharm.201282231633110.1016/j.ejpb.2012.07.015 22906708
     [Google Scholar]
  18. WagnerA.M. GranM.P. PeppasN.A. Designing the new generation of intelligent biocompatible carriers for protein and peptide delivery.Acta Pharm. Sin. B20188214716410.1016/j.apsb.2018.01.013 29719776
     [Google Scholar]
  19. ChaiQ. JiaoY. YuX. Hydrogels for biomedical applications: Their characteristics and the mechanisms behind them.Gels201731610.3390/gels3010006 30920503
     [Google Scholar]
  20. StanislawskaI. LiwinskaW. LypM. StojekZ. ZabostE. Recent advances in degradable hybrids of biomolecules and NGs for targeted delivery.Molecules20192410187310.3390/molecules24101873 31096669
     [Google Scholar]
  21. KondiahP.P.D. ChoonaraY.E. TomarL.K. TyagiC. KumarP. du ToitL.C. MarimuthuT. ModiG. PillayV. Development of a gastric absorptive, immediate responsive, oral protein-loaded versatile polymeric delivery system.AAPS PharmSciTech20171872479249310.1208/s12249‑017‑0725‑1 28205143
     [Google Scholar]
  22. UllahF. OthmanM.B.H. JavedF. AhmadZ. Md AkilH. Classification, processing and application of hydrogels: A review.Mater. Sci. Eng. C2015575741443310.1016/j.msec.2015.07.053 26354282
     [Google Scholar]
  23. GuptaP. VermaniK. GargS. Hydrogels: from controlled release to pH-responsive drug delivery.Drug Discov. Today200271056957910.1016/S1359‑6446(02)02255‑9 12047857
     [Google Scholar]
  24. HuJ. ChenY. LiY. ZhouZ. ChengY. A thermo-degradable hydrogel with light-tunable degradation and drug release.Biomaterials201711213314010.1016/j.biomaterials.2016.10.015 27760397
     [Google Scholar]
  25. MansoorS. KondiahP.P.D. ChoonaraY.E. Advanced hydrogels for the controlled delivery of insulin.Pharmaceutics20211312211310.3390/pharmaceutics13122113 34959394
     [Google Scholar]
  26. ĆujićN. TrifkovićK. BugarskiB. IbrićS. PljevljakušićD. ŠavikinK. Chokeberry (Aronia melanocarpa L.) extract loaded in alginate and alginate/inulin system.Ind. Crops Prod.20168612013110.1016/j.indcrop.2016.03.045
     [Google Scholar]
  27. LiuD. ZhaoK. QiM. LiS. XuG. WeiJ. HeX. Preparation of protein molecularimprinted polysiloxane membrane using calcium alginate film as matrix and its application for cell culture.Polymers201810217010.3390/polym10020170 30966206
     [Google Scholar]
  28. ApoorvaA. RameshbabuA.P. DasguptaS. DharaS. PadmavatiM. Novel pH-sensitive alginate hydrogel delivery system reinforced with gum tragacanth for intestinal targeting of nutraceuticals.Int. J. Biol. Macromol.202014767568710.1016/j.ijbiomac.2020.01.027 31926225
     [Google Scholar]
  29. GeorgeM. AbrahamT.E. pH sensitive alginate-guar gum hydrogel for the controlled delivery of protein drugs.Int. J. Pharm.20073351-212312910.1016/j.ijpharm.2006.11.009 17147980
     [Google Scholar]
  30. ZhangJ. WangQ. WangA. In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.Acta Biomater.20106244545410.1016/j.actbio.2009.07.001 19596091
     [Google Scholar]
  31. KarewiczA. ZasadaK. SzczubiałkaK. ZapotocznyS. LachR. NowakowskaM. “Smart” alginate-hydroxypropylcellulose microbeads for controlled release of heparin.Int. J. Pharm.20103851-216316910.1016/j.ijpharm.2009.10.021 19840839
     [Google Scholar]
  32. TripathyT. PandeyS.R. KarmakarN.C. BhagatR.P. SinghR.P. Novel flocculating agent based on sodium alginate and acrylamide.Eur. Polym. J.199935112057207210.1016/S0014‑3057(98)00284‑5
     [Google Scholar]
  33. PatelG.M. PatelC.P. TrivediH.C. Ceric-induced grafting of methyl acrylate onto sodium salt of partially carboxymethylated sodium alginate.Eur. Polym. J.199935220120810.1016/S0014‑3057(98)00123‑2
     [Google Scholar]
  34. IşıklanN. KurşunF. İnalM. Graft copolymerization of itaconic acid onto sodium alginate using benzoyl peroxide.Carbohydr. Polym.201079366567210.1016/j.carbpol.2009.09.021
     [Google Scholar]
  35. PourjavadiA. Zohuriaan-MehrM. J. Modification of carbohydrate polymers via grafting in air. 2. Ceric-initiated graft copolymerization of acrylonitrile onto natural and modified polysaccharides.Starch/Staerke.20025410482488
     [Google Scholar]
  36. ElsayedN.H. MonierM. AlatawiR.A.S. Synthesis and characterization of photo-crosslinkable 4-styryl-pyridine modified alginate.Carbohydr. Polym.201614512113110.1016/j.carbpol.2016.03.006 27106159
     [Google Scholar]
  37. QiuY. ParkK. Environment-sensitive hydrogels for drug delivery.Adv. Drug Deliv. Rev.200153332133910.1016/S0169‑409X(01)00203‑4 11744175
     [Google Scholar]
  38. IşıklanN. KurşunF. Synthesis and characterization of graft copolymer of sodium alginate and poly(itaconic acid) by the redox system.Polym. Bull.20137031065108410.1007/s00289‑012‑0876‑x
     [Google Scholar]
  39. SalisuA. SanagiM.M. Abu NaimA. Abd KarimK.J. Wan IbrahimW.A. AbdulganiyuU. Alginate graft polyacrylonitrile beads for the removal of lead from aqueous solutions.Polym. Bull.201673251953710.1007/s00289‑015‑1504‑3
     [Google Scholar]
  40. García-AstrainC. AvérousL. Synthesis and evaluation of functional alginate hydrogels based on click chemistry for drug delivery applications.Carbohydr. Polym.201819027128010.1016/j.carbpol.2018.02.086 29628248
     [Google Scholar]
  41. SoaresJ.P. Dos SantosJ.E. ChiericeG.O. Cavalheiro, É.T.G. Thermal behavior of alginic acid and its sodium salt. Eclét.Quím2004292576310.26850/1678‑4618eqj.v29.2.2004.p57‑63
     [Google Scholar]
  42. SegatoM.P. Cavalheiro, É.T.G Thermal analysis of ammonium, mono-, di- and triethanolammonium alginates.J. Therm. Anal. Calorim.200787373774110.1007/s10973‑006‑7753‑5
     [Google Scholar]
  43. DinuV. YakubovG.E. LimM. HurstK. AdamsG.G. HardingS.E. FiskI.D. Mucin immobilization in calcium alginate: A possible mucus mimetic tool for evaluating mucoadhesion and retention of flavour.Int. J. Biol. Macromol.201913883183610.1016/j.ijbiomac.2019.07.148 31351956
     [Google Scholar]
  44. EiseltP. YehJ. LatvalaR.K. SheaL.D. MooneyD.J. Porous carriers for biomedical applications based on alginate hydrogels.Biomaterials200021191921192710.1016/S0142‑9612(00)00033‑8 10941913
     [Google Scholar]
  45. DurkutS. ElçinY.M. Synthesis and characterization of thermosensitive poly(N ‐Vinyl Caprolactam)‐grafted‐aminated alginate hydrogels.Macromol. Chem. Phys.20202212190041210.1002/macp.201900412
     [Google Scholar]
  46. MatyashM. DespangF. IkonomidouC. GelinskyM. Swelling and mechanical properties of alginate hydrogels with respect to promotion of neural growth.Tissue Eng. Part C Methods201420540141110.1089/ten.tec.2013.0252 24044417
     [Google Scholar]
/content/journals/cos/10.2174/0115701794210967231016055949
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Synthesis and Characterization of Novel pH-Responsive Aminated Alginate Derivatives Hydrogels for Tissue Engineering and Drug Delivery
Curr. Org. Synth. 22, 90 (2025); https://doi.org/10.2174/0115701794210967231016055949
/content/journals/cos/10.2174/0115701794210967231016055949
/content/journals/cos/10.2174/0115701794210967231016055949
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  • Article Type:     Research Article
Keyword(s): acid-catalyzed acetalization; characterization; D-mannuronic acid; pH-responsive hydrogel; Sodium alginate; stimulus-sensitive polymers; synthesis

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