Colloid and Polymer Science

, Volume 297, Issue 4, pp 613–621 | Cite as

Preparation of multiresponsive nanogels and their controlled release properties

  • Sixiang Yuan
  • Xueting Li
  • Xiaodi Shi
  • Xihua LuEmail author
Original Contribution


Multiresponsive nanogels, which are sensitive to pH/temperature/glucose concentration have been synthesized by using N,N-diethylacrylamide (DEA) and 4-vinylphenylboronic acid (VPBA) as reaction monomer. The influence of the VPBA/DEA feeding ratio and emulsifier concentration on the as-prepared nanogel’s size and size distribution was investigated. Under the optimized condition, the diameter of the as-prepared P(DEA-co-VPBA) nanogel was 186.9 nm with excellent monodispersity (PDI 0.005); its entrapment efficiency reached 88.67% and loading efficiency of insulin reached 17.73%. The release rate of insulin loaded in the P(DEA-co-VPBA) nanogels could be adjusted by glucose concentration, which could adjust and control the blood glucose concentration in a stable concentration range intelligently. The multiresponsive nanogels could potentially be used in the fields of self-regulated drug delivery systems, real-time optical diagnosis, and monitoring of the response to treatment.


N,N-Diethylacrylamide (DEA) Vinylphenylboronic acid (VPBA) Nanogels Glucose Drug release 


Funding information

This work was financially supported by the National Natural Science Foundation of China (51473032 and 51503034).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.


  1. 1.
    American diabetes Association (2008) Diagnosis and classification of diabetes mellitus. Recenti Prog Med 101(7–8):274–276Google Scholar
  2. 2.
    Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103(2):137–149CrossRefGoogle Scholar
  3. 3.
    Grassi G (2012) Terapia insulinica bisogni insoddisfatti e nuove prospettive. Dialogos 15(3):3–9Google Scholar
  4. 4.
    Veiseh O, Tang BC, Whitehead KA, Anderson DG, Langer R (2015) Managing diabetes with nanomedicine: challenges and opportunities. Nat Rev Drug Discov 14(1):45–47CrossRefPubMedGoogle Scholar
  5. 5.
    Ravaine V, Ancla C, Catargi B (2008) Chemically controlled closed-loop insulin delivery. J Control Release 132(1):2–11CrossRefPubMedGoogle Scholar
  6. 6.
    Veiseh O, Langer R (2015) Diabetes: a smart insulin patch. Nature 524(7563):39–40CrossRefPubMedGoogle Scholar
  7. 7.
    Mccoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA (2012) Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 35(9):1897–1901CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Yang J, Cao Z (2017) Glucose-responsive insulin release: analysis of mechanisms, formulations, and evaluation criteria. J Control Release 263(2017):231–239CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Li J, Chu MKL, Gordijo CR, Abbasi AZ, Chen K, Adissu HA, Löhn MG, Adria P, Oliver W, Xiao Y (2015) Microfabricated microporous membranes reduce the host immune response and prolong the functional lifetime of a closed-loop insulin delivery implant in a type 1 diabetic rat model. Biomaterials 47(2015):51–61CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang Y, Guan Y, Zhou S (2006) Synthesis and volume phase transitions of glucose-sensitive microgels. Biomacromolecules 7(11):3196–3201CrossRefPubMedGoogle Scholar
  11. 11.
    Rong M, Li H (2013) Parameter study of glucose-sensitive hydrogel: effect of immobilized glucose oxidase on diffusion and deformation. Soft Materials 11(1):69–74CrossRefGoogle Scholar
  12. 12.
    Zhou X, Liu Z, Ma D, Xue W (2015) Glucose-sensitive nanogel for controlled release of insulin and its blood safety. J Control Release 213(2015):28CrossRefGoogle Scholar
  13. 13.
    Chen XM, Johnson A, Dordick JS, Rethwisch DG (1994) Chemoenzymatic synthesis of linear poly(sucrose acrylate): optimization of enzyme activity and polymerization conditions. Macromol Chem Phys 195(11):3567–3578CrossRefGoogle Scholar
  14. 14.
    Martin BD, Ampofo SA, Linhardt RJ, Dordick JS (1992) Biocatalytic synthesis of sugar-containing polyacrylate-based hydrogels. Macromolecules 25(26):7081–7085CrossRefGoogle Scholar
  15. 15.
    Gerhard K, Jürgen V, Horst S (1995) Hydrogels based on 3-O-acryloyl-1,2; 5,6-di-O-iso-propylidene-α-D(-)-glucofuranose. Angew Makromol Chem 228(1):59–72CrossRefGoogle Scholar
  16. 16.
    Zhou WJ, Kurth MJH, You LK, John M (2015) Synthesis and thermal properties of a novel lactose-containing poly(N-isopropylacrylamide-co-acrylamidolactamine) hydrogel. J Polym Sci A Polym Chem 37(10):1393–1402CrossRefGoogle Scholar
  17. 17.
    Patil NS, Li YZ, Rethwisch DG, Dordick JS (2015) Sucrose diacrylate: a unique chemically and biologically degradable crosslinker for polymeric hydrogels. J Polym Sci A Polym Chem 35(11):2221–2229CrossRefGoogle Scholar
  18. 18.
    Zamora M, Strumia M, Bertorello H (1996) Preparation of new gels derived from poly(sucrose acrylate) with immobilized Cibacron blue and their application in affinity chromatography. Polym Bull 37(4):483–488CrossRefGoogle Scholar
  19. 19.
    Wulff G (1995) Molecular imprinting in cross-linked materials with the aid of molecular templates- a way towards artificial antibodies. Cheminform 34(17):1812–1832Google Scholar
  20. 20.
    Liu X, Dordick JS (2015) Sugar acrylate-based polymers as chiral molecularly imprintable hydrogels. J Polym Sci A Polym Chem 37(11):1665–1671CrossRefGoogle Scholar
  21. 21.
    Rohr T, Knaus S, Sherrington DC, Gruber H (2010) Synthesis of sugar-containing hydrophilic porous polymer supports via suspension polymerization. Acta Polym 50(8):286–292CrossRefGoogle Scholar
  22. 22.
    Zhao Y, Shen Y (2016) Nanostructured hydrogels for diabetic management. Wiley-VCH Verlag GmbH & Co KGaA, pp 387–419Google Scholar
  23. 23.
    Wu W, Mitra N, Yan EC, Zhou S (2010) Multifunctional hybrid nanogel for integration of optical glucose sensing and self-regulated insulin release at physiological pH. ACS Nano 4(8):4831–4839CrossRefPubMedGoogle Scholar
  24. 24.
    Wang H, Yi J, Yu Y, Zhou S (2017) NIR upconversion fluorescence glucose sensing and glucose-responsive insulin release of carbon dot-immobilized hybrid microgels at physiological pH. Nanoscale 9(2):509–516CrossRefPubMedGoogle Scholar
  25. 25.
    Tuncel A, Ozdemir A (2000) Thermally reversible VPBA-NIPAM copolymer gels for nucleotid adsorption. J Biomater Sci Polym Ed 11(8):817–831CrossRefPubMedGoogle Scholar
  26. 26.
    Jiang G, Jiang T, Chen H, Li L, Liu YK, Zhou HJ, Feng Y, Zhou JH (2015) Preparation of multi-responsive micelles for controlled release of insulin. Colloid Polym Sci 293(1):209–215CrossRefGoogle Scholar
  27. 27.
    Du X, Jiang G, Li L, Liu YK, Chen H, Huang Q (2015) Photo-induced synthesis glucose-responsive carriers for controlled release of insulin in vitro. Colloid Polym Sci 293(7):2129–2135CrossRefGoogle Scholar
  28. 28.
    Li L, Jiang G, Yu W, Liu DP, Chen H, Liu YK, Huang Q, Tong ZZ, Yao J, Kong XD (2016) A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin. Mater Sci Eng C Mater Biol Appl 69(2016):37–45CrossRefPubMedGoogle Scholar
  29. 29.
    Du X, Jiang G, Li L, Yang WT, Chen H, Liu YK, Huang Q (2016) Preparation of glucose-sensitive and fluorescence micelles via a combination of photoinitiated polymerization and chemoenzymatic transesterification for the controlled release of insulin. J Appl Polym Sci 133(9):75766–75772CrossRefGoogle Scholar
  30. 30.
    Du X, Jiang G, Li L, Yang WT, Chen H, Liu YK, Huang Q (2015) Preparation of glucose-sensitive and fluorescence micelles via a combination of photoinitiated polymerization and chemoenzymatic transesterification for the controlled release of insulin. RSC Adv 5(92):75766–75772CrossRefGoogle Scholar
  31. 31.
    Maestas RR, Prieto JR, Kuehn GD, Hageman JH (1980) Polyacrylamide-boronate beads saturated with biomolecules: a new general support for affinity chromatography of enzymes. J Chromatogr A 189(2):225–231CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sixiang Yuan
    • 1
  • Xueting Li
    • 1
  • Xiaodi Shi
    • 1
  • Xihua Lu
    • 1
    Email author
  1. 1.College of Chemistry, Chemical Engineering and BiotechnologyDonghua UniversityShanghaiPeople’s Republic of China

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