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Exploring the conditions to generate alginate nanogels

  • Review Paper: Sol-gel, hybrids and solution chemistries
  • Published:
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Abstract

Alginate-based hydrogels are being produced worldwide for a broad spectrum of biotechnological applications, from biomedicine to agriculture. In particular, nanosized alginate-based particles have emerged as promising platforms mainly for drug delivery applications. In view of their size they can be delivered in a minimally invasive manner, and being structurally similar to the extracellular matrix of many tissues they freely diffuse to the target cells. The mild conditions of the sol-gel process are intrinsically adapted for the development of applications that require the inclusion of bio-entities during synthesis. However, one of the limitations of these systems is the fast gelling rate that hinders an adequate inclusion of bioactive molecules in nano-size hydrogel systems. In this work, we present a literature review and explore the classical theoretical work on sol-gel chemistry of alginates to discuss the range of conditions in which alginate sol-gel processes can be controlled, aiming at nanogel preparation.

Highlights

  • The design and characterization of alginate nanosized gels for biomedical applications is revised.

  • We review the classical theoretical work on sol-gel chemistry of alginates.

  • The range of conditions in which alginate cross-linking can lead to a stable nanogel are discussed.

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References

  1. Innocenzi P (2020) Understanding sol-gel transition through a picture. A short tutorial. J Sol Gel Sci Technol 94:544–550. https://doi.org/10.1007/s10971-020-05243-w

  2. Haring AP, Singh M, Koh M, et al (2020) Real-time characterization of hydrogel viscoelastic properties and sol-gel phase transitions using cantilever sensors transitions using cantilever sensors. J Rheology 64:837–850. https://doi.org/10.1122/8.0000009

  3. Derkach SR, Kuchina YA, Kolotova DS, Voron NG (2020) Polyelectrolyte polysaccharide-gelatin complexes: rheology and structure. Polymers 12:266–280. https://doi.org/10.3390/polym12020266

    Article  CAS  Google Scholar 

  4. Qin C, Zhou J, Zhang Z, et al (2018) Convenient one-step approach based on stimuli-responsive sol-gel transition properties to directly build chitosan-alginate core-shell beads. Food Hydrocoll. https://doi.org/10.1016/j.foodhyd.2018.08.001

  5. Cun I, Jureti M, Lovri J, et al (2017) Lipid/alginate nanoparticle-loaded in situ gelling system tailored for dexamethasone nasal delivery. 533:480–487. https://doi.org/10.1016/j.ijpharm.2017.05.065

  6. Drury JL, Mooney DJ (2003) Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials 24:4337–4351. https://doi.org/10.1016/S0142-9612(03)00340-5

    Article  CAS  Google Scholar 

  7. Sabra MW (2001) Bacterial alginate: physiology, product quality and process aspects. 315–325. https://doi.org/10.1007/s002530100699

  8. Ingar K, Skja G (2006) Similarities and differences between alginic acid gels and ionically crosslinked alginate gels. 20:170–175. https://doi.org/10.1016/j.foodhyd.2004.03.009

  9. Nikniaz H, Zandieh Z, Nouri M et al. (2021) Comparing various protocols of human and bovine ovarian tissue decellularization to prepare extracellular matrix-alginate scaffold for better follicle development in vitro. BMC Biotechnol 21:1–8. https://doi.org/10.1186/s12896-020-00658-3

    Article  CAS  Google Scholar 

  10. Goldberg M, Langer R, Jia X (2007) Nanostructured materials for applications in drug delivery and tissue engineering. J Biomater Sci Polym Ed 18:241–268. https://doi.org/10.1163/156856207779996931

    Article  CAS  Google Scholar 

  11. Gombotz WR, Wee SF (1998) Protein release from alginate matrices. Adv Drug Deliv Rev 31:267–285. https://doi.org/10.1016/S0169-409X(97)00124-5

    Article  CAS  Google Scholar 

  12. Gasperini L, Mano JF, Reis RL (2014) Natural polymers for the microencapsulation of cells. J R Soc Interface 11. https://doi.org/10.1098/rsif.2014.0817

  13. Perullini M, Calcabrini M, Jobbágy M, Bilmes SA (2015) Alginate/porous silica matrices for the encapsulation of living organisms: tunable properties for biosensors, modular bioreactors, and bioremediation devices. Mesoporous Biomater 2:3–12. https://doi.org/10.1515/mesbi-2015-0003

    Article  Google Scholar 

  14. Perullini M, Jobbágy M, Mouso N et al. (2010) Silica-alginate-fungi biocomposites for remediation of polluted water. J Mater Chem 20:6479. https://doi.org/10.1039/c0jm01144d

    Article  CAS  Google Scholar 

  15. Perullini M, Ferro Y, Durrieu C, et al (2014) Sol-gel silica platforms for microalgae-based optical biosensors. J Biotechnol 179. https://doi.org/10.1016/j.jbiotec.2014.02.007

  16. Perullini M, Rivero M, Jobbágy M et al. (2007) Plant cell proliferation inside an inorganic host. J Biotechnol 127:542–548. https://doi.org/10.1016/j.jbiotec.2006.07.024

    Article  CAS  Google Scholar 

  17. Perullini M, Jobbágy M, Soler-Illia GJAA, Bilmes SA (2005) Cell growth at cavities created inside silica monoliths synthesized by sol-gel. Chem Mater 17:3806–3808. https://doi.org/10.1021/cm050863x

    Article  CAS  Google Scholar 

  18. Perullini M, Orias F, Durrieu C, et al (2014) Co-encapsulation of Daphnia magna and microalgae in silica matrices, a stepping stone toward a portable microcosm. Biotechnol Reports 4. https://doi.org/10.1016/j.btre.2014.10.002

  19. Wang S, Guo Z (2014) Bio-inspired encapsulation and functionalization of living cells with artificial shells. Colloids Surf B Biointerfaces 113:483–500. https://doi.org/10.1016/j.colsurfb.2013.09.024

    Article  CAS  Google Scholar 

  20. Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 60:1638–1649. https://doi.org/10.1016/j.addr.2008.08.002

    Article  CAS  Google Scholar 

  21. Oh JK, Drumright R, Siegwart DJ, Matyjaszewski K (2008) The development of microgels/nanogels for drug delivery applications. Prog Polym Sci 33:448–477. https://doi.org/10.1016/j.progpolymsci.2008.01.002

    Article  CAS  Google Scholar 

  22. Hennink WE, van Nostrum CF (2012) Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev 64:223–236. https://doi.org/10.1016/j.addr.2012.09.009

    Article  Google Scholar 

  23. Jiang Y, Chen J, Deng C et al. (2014) Click hydrogels, microgels and nanogels: Emerging platforms for drug delivery and tissue engineering. Biomaterials 35:4969–4985. https://doi.org/10.1016/j.biomaterials.2014.03.001

    Article  CAS  Google Scholar 

  24. Molina M, Asadian-Birjand M, Balach J et al. (2015) Stimuli-responsive nanogel composites and their application in nanomedicine. Chem Soc Rev 44:6161–6186. https://doi.org/10.1039/c5cs00199d

    Article  CAS  Google Scholar 

  25. Raemdonck K, Demeester J, De Smedt S (2009) Advanced nanogel engineering for drug delivery. Soft Matter 5:707–715. https://doi.org/10.1039/b811923f

    Article  CAS  Google Scholar 

  26. Merino S, Martín C, Kostarelos K et al. (2015) Nanocomposite hydrogels: 3D polymer-nanoparticle synergies for on-demand drug delivery. ACS Nano 9:4686–4697. https://doi.org/10.1021/acsnano.5b01433

    Article  CAS  Google Scholar 

  27. Rondeau E, Cooper-White JJ (2008) Biopolymer microparticle and nanoparticle formation within a microfluidic device. Langmuir 24:6937–6945. https://doi.org/10.1021/la703339u

    Article  CAS  Google Scholar 

  28. Sonego JM, Santagapita PR, Perullini M, Jobbágy M (2016) Ca(II) and Ce(III) homogeneous alginate hydrogels from the parent alginic acid precursor: a structural study. Dalt Trans 45. https://doi.org/10.1039/c6dt00321d

  29. Zazzali I, Aguirre Calvo TR, Pizones Ruíz-Henestrosa VM, et al (2019) Effects of pH, extrusion tip size and storage protocol on the structural properties of Ca(II)-alginate beads. Carbohydr Polym 206: https://doi.org/10.1016/j.carbpol.2018.11.051

  30. Aguirre Calvo TR, Perullini M, Santagapita PR (2018) Encapsulation of betacyanins and polyphenols extracted from leaves and stems of beetroot in Ca(II)-alginate beads: A structural study. J Food Eng 235. https://doi.org/10.1016/j.jfoodeng.2018.04.015

  31. Schuster E, Cucheval A, Lundin L, Williams MAK (2011) Using SAXS to reveal the degree of bundling in the polysaccharide junction zones of microrheologically distinct pectin gels. Biomacromolecules 12:2583–2590. https://doi.org/10.1021/bm200578d

    Article  CAS  Google Scholar 

  32. Traffano-Schiffo MV, Castro-Giraldez M, Fito PJ, et al (2018) Gums induced microstructure stability in Ca(II)-alginate beads containing lactase analyzed by SAXS. Carbohydr Polym 179. https://doi.org/10.1016/j.carbpol.2017.09.096

  33. Paredes Juárez GA, Spasojevic M, Faas MM, de Vos P (2014) Immunological and technical considerations in application of alginate-based microencapsulation systems. Front Bioeng Biotechnol 2:1–15. https://doi.org/10.3389/fbioe.2014.00026

    Article  Google Scholar 

  34. Agulhon P, Robitzer M, David L, Quignard F (2012) Structural regime identification in ionotropic alginate gels: Influence of the cation nature and alginate structure. Biomacromolecules 13:215–220. https://doi.org/10.1021/bm201477g

    Article  CAS  Google Scholar 

  35. Wang Z-Y, Zhang Q-Z, Konno M, Saito S (1993) Sol–gel transition of alginate solution by the addition of various divalent cations: 13C-nmr spectroscopic study. Biopolymers 33:703–711. https://doi.org/10.1002/bip.360330419

    Article  CAS  Google Scholar 

  36. Cao L, Lu W, Mata A et al. (2020) Egg-box model-based gelation of alginate and pectin: a review. Carbohydr Polym 242:116389. https://doi.org/10.1016/j.carbpol.2020.116389

    Article  CAS  Google Scholar 

  37. Wang Z‐Y, Zhang Q‐Z, Konno M, Saito S (1994) Sol–gel transition of alginate solution by the addition of various divalent cations: a rheological study. Biopolymers 34:737–746. https://doi.org/10.1002/bip.360340606

    Article  CAS  Google Scholar 

  38. Yang CH, Wang MX, Haider H et al. (2013) Strengthening alginate/polyacrylamide hydrogels using various multivalent cations. ACS Appl Mater Interfaces 5:10418–10422. https://doi.org/10.1021/am403966x

    Article  CAS  Google Scholar 

  39. Wang ZY, Zhang QZ, Konno M, Saito S (1991) Sol-gel transition of alginate solution by additions of various divalent cations: critical behavior of relative viscosity. Chem Phys Lett 186:463–466. https://doi.org/10.1016/0009-2614(91)90210-Z

    Article  CAS  Google Scholar 

  40. Sabra S, Abdelmoneem M, Abdelwakil M et al. (2017) Self-assembled nanocarriers based on amphiphilic natural polymers for anti- cancer drug delivery applications. Curr Pharm Des 23:5213–5229. https://doi.org/10.2174/1381612823666170526111029

    Article  CAS  Google Scholar 

  41. Varshosaz J, Taymouri S, Ghassami E (2017) Supramolecular self-assembled nanogels a new platform for anticancer drug delivery. Curr Pharm Des 23:5242–5260. https://doi.org/10.2174/1381612823666170710121900

    Article  CAS  Google Scholar 

  42. Addisu KD, Hailemeskel BZ, Mekuria SL et al. (2018) Bioinspired, manganese-chelated alginate-polydopamine nanomaterials for efficient in vivo T1-weighted magnetic resonance imaging. ACS Appl Mater Interfaces 10:5147–5160. https://doi.org/10.1021/acsami.7b13396

    Article  CAS  Google Scholar 

  43. Li P, Luo Z, Liu P et al. (2013) Bioreducible alginate-poly(ethylenimine) nanogels as an antigen-delivery system robustly enhance vaccine-elicited humoral and cellular immune responses. J Control Release 168:271–279. https://doi.org/10.1016/j.jconrel.2013.03.025

    Article  CAS  Google Scholar 

  44. De Santis S, Diociaiuti M, Cametti C, Masci G (2014) Hyaluronic acid and alginate covalent nanogels by template cross-linking in polyion complex micelle nanoreactors. Carbohydr Polym 101:96–103. https://doi.org/10.1016/j.carbpol.2013.09.033

    Article  CAS  Google Scholar 

  45. Bazban-Shotorbani S, Dashtimoghadam E, Karkhaneh A et al. (2016) Microfluidic directed synthesis of alginate nanogels with tunable pore size for efficient protein delivery. Langmuir 32:4996–5003. https://doi.org/10.1021/acs.langmuir.5b04645

    Article  CAS  Google Scholar 

  46. Xue Y, Xia X, Yu B et al. (2015) A green and facile method for the preparation of a pH-responsive alginate nanogel for subcellular delivery of doxorubicin. RSC Adv 5:73416–73423. https://doi.org/10.1039/c5ra13313k

    Article  CAS  Google Scholar 

  47. Wang Z-Y, Zhang Q-Z, Konno M, Saito S (1993) Sol-gel transition of alginate solution by addition of calcium ions: alginate concentration dependence of gel point. J Phys II 3:1–7. https://doi.org/10.1051/jp2:1993105

    Article  CAS  Google Scholar 

  48. Flórez-Castillo JM, Ropero-Vega JL, Perullini M, Jobbágy M (2019) Biopolymeric pellets of polyvinyl alcohol and alginate for the encapsulation of Ib-M6 peptide and its antimicrobial activity against E. coli. Heliyon 5. https://doi.org/10.1016/j.heliyon.2019.e01872

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Acknowledgements

MP wants to dedicate this paper to the memory of Vicente Povse from whom she has largely profited from fruitful discussions about the coordination chemistry of different cations with alginates. This work was supported by funds from the National Scientific and Technological Research Council of Argentina (CONICET), PIP 11220170100991CO.

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Authors and Affiliations

  1. Departamento de Química Inorgánica, Analítica y Química Física (DQIAQF), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

    Brianne Salvati & Mercedes Perullini

  2. CONICET-Universidad de Buenos Aires. Instituto de Química de Materiales medio Ambiente y Energía (INQUIMAE), Buenos Aires, Argentina

    Brianne Salvati & Mercedes Perullini

  3. Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

    Patricio Santagapita

  4. CONICET-Universidad de Buenos Aires. Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR), Buenos Aires, Argentina

    Patricio Santagapita

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  1. Brianne Salvati
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  2. Patricio Santagapita
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  3. Mercedes Perullini
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Correspondence to Mercedes Perullini.

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Salvati, B., Santagapita, P. & Perullini, M. Exploring the conditions to generate alginate nanogels. J Sol-Gel Sci Technol 102, 142–150 (2022). https://doi.org/10.1007/s10971-021-05631-w

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  • DOI: https://doi.org/10.1007/s10971-021-05631-w

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