Supramolecular host–guest carrier based on maltose-modified hyperbranched polymer and polyelectrolyte multilayers: toward stable and reusable glucose biosensor


Regards to the global prevalence of diabetes, clinical management should tackle the awkwardness of continuous glucose monitoring systems (CGMS). Although CGMS are commercially accepted, they are still suffering due to their low sustainability and reusability. One method to circumvent these shortcomings is the immobilization of enzymes onto stable carriers. In this contribution, our aim was to build up a highly stable and reproducible enzyme-based host–guest carrier from maltose-modified hyperbranched poly(ethylene imine) (PEI-Mal-C) and polyelectrolyte multilayers (PEMs) to monitor glucose level. Thus, enzymes, such as glucose oxidase (GOx) and horseradish peroxide (POx), were immobilized in core–shell PEI-Mal-C and highly packaged in carrier-based PEM. Herein, the PEM was created using the layer-by-layer protocol, where a consecutive deposition of polyions was achieved. Therein, the polycation PEI-Mal-C was alternatively deposited with different polyanions, e.g., poly(acrylic acid) and heparin (HE), on a solid substrate. The enzyme immobilization, leaching and enzymatic activity were investigated through different modules, including ultraviolet–visible (UV–Vis) spectrophotometer, rheometer, X-ray spectroscopy, contact angle meter, atomic force microscopy and conductometer. To conclude, our approach enabled the use of immobilized GOx/POx for more than one time with the significantly similarly fitted regression calibration curve. It is implied that this work will be the first step to construct a stable hyperbranched glyconanomaterial-immobilized enzyme based on assembled multilayers, with the potential to be applied in a stable and reusable biosensor.

This is a preview of subscription content, access via your institution.

Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12


  1. 1.

    Chen C, Zhao X-L, Li Z-H, Zhu Z-G, Qian S-H, Flewitt AJ (2017) Continuous glucose monitoring (CGM) in very low birth weight newborns needing parenteral nutrition: validation and glycemic percentiles. Sensor 17:182

    Article  Google Scholar 

  2. 2.

    Schuster KM, Barre K, Inzucchi SE, Udelsman R, Davis KA (2014) Continuous glucose monitoring in the surgical intensive care unit: concordance with capillary glucose. J Trauma Acute Care Surg 76:798

    CAS  Article  Google Scholar 

  3. 3.

    Gough DA, Kumosa LS, Routh TL, Lin JT, Lucisano JY (2010) Function of an implanted tissue glucose sensor for more than 1 year in animals. Sci Transl Med 2:42ra53

    Article  Google Scholar 

  4. 4.

    Bruen D, Delaney C, Florea L, Diamond D (2017) Glucose sensing for diabetes monitoring: recent developments. Sensors 17:1866

    Article  Google Scholar 

  5. 5.

    Bailey T, Bode BW, Christiansen MP, Klaff LJ, Alva S (2015) The performance and usability of a factory-calibrated flash glucose monitoring system. Diabetes Technol Ther 17:787

    CAS  Article  Google Scholar 

  6. 6.

    Harris JM, Reyes C, Lopez GPJ (2013) Common causes of glucose oxidase instability in vivo biosensing: a brief review. Diabetes Sci Technol 7:1030

    Article  Google Scholar 

  7. 7.

    Decher G (1997) Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science 277:1232

    CAS  Article  Google Scholar 

  8. 8.

    Decher G, Hong JD, Schmitt J (1992) Buildup of ultrathin multilayer films by a self-assembly process: III. Consecutively alternating adsorption of anionic and cationic polyelectrolytes on charged surfaces. Thin Solid Films 210–211(Part 2):831

    Article  Google Scholar 

  9. 9.

    Zhang J, Senger B, Vautier D, Picart C, Schaaf P, Voegel JC, Lavalle P (2005) Natural polyelectrolyte films based on layer-by layer deposition of collagen and hyaluronic acid. Biomaterials 26:3353

    CAS  Article  Google Scholar 

  10. 10.

    Sukhishvili SA, Kharlampieva E, Izumrudov V (2006) Where polyelectrolyte multilayers and polyelectrolyte complexes meet. Macromolecules 39:8873

    CAS  Article  Google Scholar 

  11. 11.

    Salem S, Müller M, Torger B, Janke A, Eichhorn KJ, Voit B, Appelhans D (2015) Glycopolymer polyelectrolyte multilayers composed of heparin and maltose-modified poly (ethylene imine) as a strong/weak polyelectrolyte system for future drug delivery coatings: influence of pH and sugar architecture on growth of multilayers and multilayer swelling and stability. Macromol Chem Phys 216:182

    CAS  Article  Google Scholar 

  12. 12.

    Salem S (2015) Glycopolymer polyelectrolyte multilayers based on maltose-modified hyperbranched poly(ethyleneimine) for future drug delivery coatings and biomedical applications. Doctoral dissertation, Saechsische Landesbibliothek-Staats-und Universitaetsbibliothek Dresden

  13. 13.

    Jimenez A, Armada MP, Losada J, Villena C, Alonso B, Casado CM (2014) Amperometric biosensors for NADH based on hyperbranched dendritic ferrocene polymers and Pt nanoparticles. Sensors Actuators B Chem 190:111

    CAS  Article  Google Scholar 

  14. 14.

    Li H, Zhao F, Yue L, Li S, Xiao F (2016) Nonenzymatic electrochemical biosensor based on novel hydrophilic ferrocene-terminated hyperbranched polymer and its application in glucose detection. Electroanalysis 28:1003

    CAS  Article  Google Scholar 

  15. 15.

    Zheng Y, Li S, Weng Z, Gao C (2015) Hyperbranched polymers: advances from synthesis to applications. Chem Soc Rev 44:4091

    CAS  Article  Google Scholar 

  16. 16.

    Caminade A-M, Yan D, Smith DK (2015) Dendrimers and hyperbranched polymers. Chem Soc Rev 44:3870

    CAS  Article  Google Scholar 

  17. 17.

    Appelhans D, Komber H, Quadir MA, Richter S, Schwarz S, van der Vlist J, Aigner A, Müller M, Loos K, Seidel J, Arndt KF (2009) Hyperbranched PEI with various oligosaccharide architectures: synthesis, characterization, ATP complexation, and cellular uptake properties. Biomacromolecules 10:1114

    CAS  Article  Google Scholar 

  18. 18.

    Gorzkiewicz M, Sztandera K, Jatczak-Pawlik I, Zinke R, Appelhans D, Klajnert-Maculewicz B, Pulaski Ł (2018) Terminal sugar moiety determines immunomodulatory properties of poly(propyleneimine) glycodendrimers. Biomacromolecules. 19:1562

    CAS  Article  Google Scholar 

  19. 19.

    Studzian M, Szulc A, Janaszewska A, Appelhans D, Pułaski Ł, Klajnert-Maculewicz B (2017) Mechanisms of Internalization of maltose-modified poly(propyleneimine) glycodendrimers into leukemic cell lines. Biomacromolecules 18:1509

    CAS  Article  Google Scholar 

  20. 20.

    Lee KM, Kim KH, Yoon H, Kim H (2018) Chemical design of functional polymer structures for biosensors: from nanoscale to macroscale. Polymers 10:551

    Article  Google Scholar 

  21. 21.

    Washko W, Rice EW (1961) Determination of glucose by an improved enzymatic procedure. Clin Chem 7:542

    CAS  Article  Google Scholar 

  22. 22.

    Wang YH, Gu HY (2009) Hemoglobin co-immobilized with silver–silver oxide nanoparticles on a bare silver electrode for hydrogen peroxide electroanalysis. Microchim Acta 164:41

    CAS  Article  Google Scholar 

  23. 23.

    Zhou M, Diwu Z, Panchuk-Voloshina N, Haugland RP (1997) A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases. Anal Biochem 253:162

    CAS  Article  Google Scholar 

  24. 24.

    Barnes HA, Hutton JF, Walters K (1989) An introduction to rheology, vol 3. Elsevier, Amsterdam

    Book  Google Scholar 

  25. 25.

    Nunez CM, Chiou B-S, Andrady AL, Khan SA (2000) Solution rheology of hyperbranched polyesters and their blends with linear polymers. Macromolecules 33:1720

    CAS  Article  Google Scholar 

  26. 26.

    Läuger J, Heiko S (2016) Effects of instrument and fluid inertia in oscillatory shear in rotational rheometers. J Rheol 60:393

    Article  Google Scholar 

  27. 27.

    Dieter GE, Bacon DJ (1986) Mechanical metallurgy. McGraw-hill, New York, p 3

    Google Scholar 

  28. 28.

    Briggs D, Beamson G (1992) Primary and secondary oxygen-induced C1s binding energy shifts in x-ray photoelectron spectroscopy of polymers. Anal Chem 64:1729

    CAS  Article  Google Scholar 

  29. 29.

    Gao C, Yan D (2004) Hyperbranched polymers: from synthesis to applications. Prog Polym Sci 29:183

    CAS  Article  Google Scholar 

  30. 30.

    Torger B, Vehlow D, Urban B, Salem S, Appelhans D, Müller M (2013) Cast adhesive polyelectrolyte complex particle films of unmodified or maltose-modified poly (ethyleneimine) and cellulose sulphate: fabrication, film stability and retarded release of zoledronate. Biointerphases 11:25

    Article  Google Scholar 

  31. 31.

    Ferry JD (1980) Viscoelastic properties of polymers. Wiley, New York

    Google Scholar 

  32. 32.

    Sunthar P (2010) Polymer rheology. Springer, New York, pp 171–191

    Google Scholar 

  33. 33.

    Frederick KR, Tung J, Emerick RS, Masiarz FR, Chamberlain SH, Vasavada AM, Rosenberg S, Chakraborty SU, Schopfer LM, Schopter LM (1990) Glucose oxidase from aspergillus niger. J Biol Chem 265:3793

    CAS  PubMed  Google Scholar 

  34. 34.

    Benavidez TE, Torrente D, Marucho M, Garcia CD (2014) Adsorption and catalytic activity of glucose oxidase accumulated on OTCE upon the application of external potential. J Colloid Interface Sci 435:164

    CAS  Article  Google Scholar 

  35. 35.

    Harris JM, Reyes C, Lopez GP (2013) Common causes of glucose oxidase instability in in vivo biosensing: a brief review. J Diabetes Sci Technol 7:1030

    Article  Google Scholar 

  36. 36.

    Nemati M, Hosseini SM, Bagheripour E, Madaeni SS (2016) Surface modification of cation exchange membranes by graft polymerization of PAA-co-PANI/MWCNTs nanoparticles. Kor J Chem Eng 33:1037

    CAS  Article  Google Scholar 

  37. 37.

    Ji J, Joh H-I, Chung Y, Kwon Y (2017) Glucose oxidase and polyacrylic acid based water swellable enzyme–polymer conjugates for promoting glucose detection. Nanoscale 9:15998

    CAS  Article  Google Scholar 

  38. 38.

    Zaldivar G, Tagliazucchi M (2016) Layer-by-layer self-assembly of polymers with pairing interactions. ACS Macro Lett 5:862

    CAS  Article  Google Scholar 

Download references


Still, the implementation of this study would not have been possible if we did not have the boost of many individuals and organizations. We are grateful to the School of Chemical Engineering and Applied Chemistry (CEAC), Aston University, Birmingham, UK, and both Prof. Brian J. Tighe and Paul D. Topham for providing facilities and equipment for achieving these goals. Moreover, we have to express our appreciation for Science and Technology Development Funds (STDF), Egypt, Newton Fund, British Council and the National Research Centre (NRC), Egypt, for their kind support of this study and providing a scholarship. All grateful thankfulness for the Department of Polymer Science, the University of Sheffield for their generous present of silicon wafers.


No financial support was provided.

Author information



Corresponding author

Correspondence to Samaa R. Salem.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 306 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Salem, S.R., Sullivan, J.L., Topham, P.D. et al. Supramolecular host–guest carrier based on maltose-modified hyperbranched polymer and polyelectrolyte multilayers: toward stable and reusable glucose biosensor. Polym. Bull. 77, 3143–3170 (2020).

Download citation


  • Carrier-based polyelectrolyte multilayers
  • Core–shell hyperbranched glycopolymer
  • Reproducibility
  • Stability
  • Coatings
  • Glucose oxidase immobilization