Colloid and Polymer Science

, Volume 296, Issue 11, pp 1905–1915 | Cite as

Synthesis and characterization of hydrolytically degradable poly(N-vinylcaprolactam) copolymers with in-chain ester groups

  • Maria Andrei
  • Paul O. Stǎnescu
  • Constantin Drǎghici
  • Livia Maria Butac
  • Mircea TeodorescuEmail author
Original Contribution


Poly(N-vinylcaprolactam) (PNVCL) is attracting increasing interest as a polymer for biomedical application. However, it is not biodegradable, which is an important drawback for such applications. The present paper describes the synthesis and characterization of novel thermosensitive PNVCL copolymers able to hydrolytically degrade, which were prepared by the RAFT/MADIX copolymerization of NVCL and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO). The RAFT/MADIX polymerization process displayed a moderate degree of control under the experimental conditions employed as proven by GPC measurements. The formation of the NVCL-BMDO copolymers was demonstrated by 1H NMR analyses which showed the presence of the in-chain ester groups resulted from the ring-opening polymerization of BMDO. The BMDO content of the copolymers was much lower than in the feed, indicating a higher reactivity of NVCL, which was confirmed through the estimation of the monomer reactivity ratios by applying the non-linear least squares method to fit the experimental results to the Lowry-Meyer integrated form of the Mayo-Lewis copolymer composition equation. The glass transition temperature of the copolymers diminished with the BMDO unit concentration within the chain. The phase transition temperature of the copolymers in 0.5-wt% aqueous solution decreased with the BMDO content as proven by transmittance measurements, in agreement with the increasing hydrophobic character. The degradability of the copolymers was demonstrated by the hydrolysis of the in-chain ester groups in 1-N KOH solution. The degraded polymer displayed a higher phase transition temperature than the original polymer, as expected. The results described within this paper may find applications for the synthesis of new biomaterials.


5,6-Benzo-2-methylene-1,3-dioxepane Poly(N-vinylcaprolactam) Thermoresponsive Degradable Reversible addition-fragmentation chain transfer polymerization Cyclic ketene acetal 


Funding information

No sources of financial funding and support were available for this work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Gil E, Hudson SH (2004) Stimuli-responsive polymers and their bioconjugates. Prog Polym Sci 29:1173–1222CrossRefGoogle Scholar
  2. 2.
    Ruel-Gariepy E, Leroux JC (2004) In situ-forming hydrogels—review of temperature-sensitive systems. Eur J Pharm Biopharm 58:409–426CrossRefGoogle Scholar
  3. 3.
    Crespy D, Rossi RM (2007) Temperature-responsive polymers with LCST in the physiological range and their applications in textiles. Polym Int 56:1461–1468CrossRefGoogle Scholar
  4. 4.
    Zhang X, Zhou L, Zhang X, Dai H (2010) Synthesis and solution properties of temperature-sensitive copolymers based on NIPAM. J Appl Polym Sci 116:1099–1105CrossRefGoogle Scholar
  5. 5.
    Lu W, Zhao B, Li N, Yao Y, Chen W (2010) Thermosensitive copolymer with cobalt phthalocyanine and catalytic behavior based on adjustable LCST. React Funct Polym 70:135–141CrossRefGoogle Scholar
  6. 6.
    Li Z, Guan J (2011) Thermosensitive hydrogels for drug delivery. Expert Opin Drug Deliv 8:991–1007CrossRefGoogle Scholar
  7. 7.
    Huynh CT, Nguyen MK, Lee DS (2011) Injectable block copolymer hydrogels: achievements and future challenges for biomedical applications. Macromolecules 44:6629–6636CrossRefGoogle Scholar
  8. 8.
    Buenger D, Topuz F, Groll J (2012) Hydrogels in sensing applications. Prog Polym Sci 37:1678–1719CrossRefGoogle Scholar
  9. 9.
    Toh WS, Loh XJ (2014) Advances in hydrogel delivery systems for tissue engineering. Mater Sci Eng C 45:690–697CrossRefGoogle Scholar
  10. 10.
    Sedlacek O, Monnery BD, Filippov SK, Hoogenboom R, Hruby M (2012) Poly(2-oxazoline)s—are they more advantageous for biomedical applications than other polymers? Macromol Rapid Commun 33:1648–1662CrossRefGoogle Scholar
  11. 11.
    Lutz JF (2011) Thermo-switchable materials prepared using the OEGMA-platform. Adv Mater 23:2237–2243CrossRefGoogle Scholar
  12. 12.
    Liu J, Debuigne A, Detrembleur C, Jérôme C (2014) Poly(N-vinylcaprolactam): a thermoresponsive macromolecule with promising future in biomedical field. Adv Healthc Mater 3:1941–1968CrossRefGoogle Scholar
  13. 13.
    Cortez-Lemus NA, Licea-Claverie A (2016) Poly(N-vinylcaprolactam), a comprehensive review on a thermoresponsive polymer becoming popular. Prog Polym Sci 53:1–51CrossRefGoogle Scholar
  14. 14.
    Sun LF, Zhuo RX, Liu ZL (2003) Studies on the synthesis and properties of temperature responsive and biodegradable hydrogels. Macromol Biosci 3:725–728CrossRefGoogle Scholar
  15. 15.
    Ren L, Agarwal S (2007) Synthesis, characterization and properties evaluation of poly[(N-isopropylacrylamide)-co-ester]s. Macromol Chem Phys 208:245–253CrossRefGoogle Scholar
  16. 16.
    Galperin A, Long TJ, Ratner BD (2010) Degradable, thermosensitive poly(N-isopropylacrylamide)-based scaffolds with controlled porosity for tissue engineering applications. Biomacromolecules 11:2583–2592CrossRefGoogle Scholar
  17. 17.
    Siegwart DJ, Bencherif SA, Srinivasan A, Hollinger JO, Matyjaszewski K (2008) Synthesis, characterization, and in vitro cell culture viability of degradable poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane)-based polymers and crosslinked gels. J Biomed Mater Res A 87:345–358CrossRefGoogle Scholar
  18. 18.
    Lutz JF, Andrieu J, Uzgun S, Rudolph C, Agarwal S (2007) Biocompatible, thermoresponsive, and biodegradable: simple preparation of “all-in-one” biorelevant polymers. Macromolecules 40:8540–8543CrossRefGoogle Scholar
  19. 19.
    Delplace V, Tardy A, Harrison S, Mura S, Gigmes D, Guillaneuf Y, Nicolas J (2013) Degradable and comb-like PEG-based copolymers by nitroxide-mediated radical ring-opening polymerization. Biomacromolecules 14:3769–3779CrossRefGoogle Scholar
  20. 20.
    Agarwal S (2010) Chemistry, chances and limitations of the radical ring-opening polymerization of cyclic ketene acetals for the synthesis of degradable polyesters. Polym Chem 1:953–964CrossRefGoogle Scholar
  21. 21.
    Tardy A, Nicolas J, Gigmes D, Lefay C, Guillaneuf Y (2017) Radical ring-opening polymerization: scope, limitations, and application to (bio)degradable materials. Chem Rev 117:1319–1406CrossRefGoogle Scholar
  22. 22.
    Komatsu S, Asoh TA, Ishihara R, Kikuchi A (2017) Facile preparation of degradable thermoresponsive polymers as biomaterials: thermoresponsive polymers prepared by radical polymerization degrade to water-soluble oligomers. Polymer 130:68–73CrossRefGoogle Scholar
  23. 23.
    Turturica G, Andrei M, Stanescu PO, Draghici C, Vuluga DM, Zaharia A, Sarbu A, Teodorescu M (2016) ABA triblock copolymers of poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane) (A) and poly(ethylene glycol) (B): synthesis and thermogelation and degradation properties in aqueous solutions. Colloid Polym Sci 294:743–753CrossRefGoogle Scholar
  24. 24.
    Andrei M, Stanescu PO, Draghici C, Teodorescu M (2017) Degradable thermosensitive injectable hydrogels with two-phase composite structure from aqueous solutions of poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane)-poly(ethylene glycol) triblock copolymers and biopolymers. Colloid Polym Sci 295:1805–1816CrossRefGoogle Scholar
  25. 25.
    Guégain E, Michel JP, Boissenot T, Nicolas J (2018) Tunable degradation of copolymers prepared by nitroxide-mediated radical ring-opening polymerization and point-by-point comparison with traditional polyesters. Macromolecules 51:724–736CrossRefGoogle Scholar
  26. 26.
    Wickel H, Agarwal S (2003) Synthesis and characterization of copolymers of 5,6-benzo-2-methylene-1,3-dioxepane and styrene. Macromolecules 36:6152–6159CrossRefGoogle Scholar
  27. 27.
    Peng H, Rübsam K, Huang X, Jakob F, Karperien M, Schwaneberg U, Pich A (2016) Reactive copolymers based on N-vinyl lactams with pyridyl disulfide side groups via RAFT polymerization and postmodification via thiol-disulfide exchange reaction. Macromolecules 49:7141–7154CrossRefGoogle Scholar
  28. 28.
    Beija M, Marty JD, Destarac M (2011) Thermoresponsive poly(N-vinylcaprolactam)-coated gold nanoparticles: sharp reversible response and easy tenability. Chem Commun 47:2826–2828CrossRefGoogle Scholar
  29. 29.
    Kobben S, Ethirajan A, Junkers T (2014) Synthesis of degradable poly(methyl methacrylate) star polymers via RAFT copolymerization with cyclic ketene acetals. J Polym Sci Part A Polym Chem 52:1633–1641CrossRefGoogle Scholar
  30. 30.
    Agarwal S, Ren L, Kissel T, Bege N (2010) Synthetic route and characterization of main chain ester-containing hydrolytically degradable poly(N,N-dimethylaminoethyl methacrylate)-based polycations. Macromol Chem Phys 211:905–915CrossRefGoogle Scholar
  31. 31.
    Gomez Ayala G, Malinconico M, Laurienzo P, Tardy A, Guillaneuf Y, Lansalot M, D’Agosto F, Charleux B (2014) RAFT/MADIX copolymerization of vinyl acetate and 5,6-benzo-2-methylene-1,3-dioxepane. J Polym Sci Part A Polym Chem 52:104–111CrossRefGoogle Scholar
  32. 32.
    Huang J, Gil R, Matyjaszewski K (2005) Synthesis and characterization of copolymers of 5,6-benzo-2-methylene-1,3-dioxepane and n-butyl acrylate. Polymer 46:11698–11706CrossRefGoogle Scholar
  33. 33.
    Agarwal S (2006) Radical ring opening and vinyl copolymerization of 2,3,4,5,6-pentafluorostyrene with 5,6-benzo-2-methylene-1,3-dioxepane:synthesis and structural characterization using 1D and 2D NMR techniques. J Polym Res 13:403–412CrossRefGoogle Scholar
  34. 34.
    Moad G, Rizzardo E, Thang SH (2008) Radical addition-fragmentation chemistry in polymer synthesis. Polymer 49:1079–1131CrossRefGoogle Scholar
  35. 35.
    Wan D, Zhou Q, Pu H, Yang G (2008) Controlled radical polymerization of N-vinylcaprolactam mediated by xanthate or dithiocarbonate. J Polym Sci Part A Polym Chem 46:3756–3765CrossRefGoogle Scholar
  36. 36.
    Dixon KW (1999) Decomposition rates of organic free radical initiators. In: Brandrup J, Immergut EH, Grulke EA (eds) Polymer handbook 4th edn. Wiley, New York, pp II/1–II/76Google Scholar
  37. 37.
    Kirsh YE, Yanul NA, Kalninsh KK (1999) Structural transformation of water associate interactions in poly-N-vinylcaprolactam-water system. Eur Polym J 35:305–316CrossRefGoogle Scholar
  38. 38.
    Meeussen F, Nies E, Berghmans H, Verbrugghe S, Goethals E, Du Prez F (2000) Phase behavior of poly(N-vinylcaprolactam) in water. Polymer 41:8597–8602CrossRefGoogle Scholar
  39. 39.
    Boyko VB (2004) N-Vinylcaprolactam based bulk and microgels: synthesis, structural formation and characterization by dynamic light scattering. Ph. D. Thesis, Faculty of Mathematic and Natural Sciences, Dresden University of Technology. . Accessed 20 April 2017
  40. 40.
    Stanescu PO, Turturica G, Andrei M, Draghici C, Vuluga DM, Zaharia A, Sarbu A, Teodorescu M (2015) Kinetic study upon the thermal degradation of poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane) statistical copolymers. Mater Plast 52:193–197Google Scholar
  41. 41.
    Maeda Y, Nakamura T, Ikeda I (2002) Hydration and phase behaviour of poly(N-vinylcaprolactam) and poly(N-vinlylpyrrolidone) in water. Macromolecules 35:217–222CrossRefGoogle Scholar
  42. 42.
    Lutz JF (2008) Polymerization of oligo(ethylene glycol) (meth)acrylates: toward new generations of smart biocompatible materials. J Polym Sci Part A Polym Chem 46:3459–3470CrossRefGoogle Scholar
  43. 43.
    van Herk AM, Dröge T (1997) Nonlinear least squares fitting applied to copolymerization modelling. Macromol Theory Simul 6:1263–1276CrossRefGoogle Scholar
  44. 44.
    Meyer VE, Lowry GG (1965) Integral and differential binary copolymerization equations. J Polym Sci Part A 3:2843–2851Google Scholar
  45. 45.
    Arehart SV, Matyjaszewski K (1999) Atom transfer radical copolymerization of styrene and n-butyl acrylate. Macromolecules 32:2221–2231CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Bioresources and Polymer Science, Faculty of Applied Chemistry and Materials SciencePolitehnica University of BucharestBucharestRomania
  2. 2.Center of Organic Chemistry of the Romanian AcademyBucharestRomania

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