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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

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Abstract

Novel hydrolytically degradable thermosensitive triblock copolymers with poly(ethylene glycol) (PEG) middle-chain and random copolymers of N-isopropylacrylamide and 5,6-benzo-2-methylene-1,3-dioxepane as side blocks were synthesized by the reversible addition–fragmentation chain transfer (RAFT) copolymerization of the two monomers in the presence of the bisester of [S-1-dodecyl-S′-(α,α′-dimethyl-α″-acetic acid)] trithiocarbonate and α,ω-dihydroxy PEG of 10,000 Da molecular weight as the RAFT macroagent. The polymers prepared were structurally characterized by gel permeation chromatography (GPC), 1H NMR and differential scanning calorimetry (DSC) analyses, and their thermosensitive behavior was evidenced by rheological measurements on 10 wt% aqueous solutions. The polymer aqueous solutions displayed enhanced viscosity at low temperatures due to the association of the hydrophobic dodecyl trithiocarbonate end groups, which was decreased by free radically removing the RAFT groups in the presence of tributyltin hydride. The gelation temperature, defined as the temperature at which the viscoelasticity moduli become equal each other, ranged between 36 and 43 °C depending on the aqueous solvent (distilled water or phosphate buffer saline (PBS)) and the presence of hydrophobic dodecyl end groups. The degradable character of the triblock copolymers prepared was proved by the hydrolysis of the in-chain ester groups in 1-N KOH solution at room temperature. A partial degradation of the polymer also occurred in the gel formed at 37 °C from a 10 wt% PBS solution, as proved by both GPC and 1H NMR measurements. Under these conditions, the gel completely dissolved and lost its thermogelation ability up to 60 °C in less than 24 days.

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References

  1. Gil E, Hudson SH (2004) Stimuli-responsive polymers and their bioconjugates. Prog Polym Sci 29:1173–1222

    Article  CAS  Google Scholar 

  2. Ruel-Gariepy E, Leroux JC (2004) In situ-forming hydrogels—review of temperature-sensitive systems. Eur J Pharm Biopharm 58:409–426

    Article  CAS  Google Scholar 

  3. Crespy D, Rossi RM (2007) Temperature-responsive polymers with LCST in the physiological range and their applications in textiles. Polym Int 56:1461–1468

    Article  CAS  Google Scholar 

  4. Guenther M, Gerlach G, Corten C, Kukling D, Müller M, Shi Z, Soerber J, Arndt KF (2007) Application of polyelectrolytic temperature-responsive hydrogels in chemical sensors. Macromol Symp 254:314–321

    Article  CAS  Google Scholar 

  5. Zhang X, Zhou L, Zhang X, Dai H (2010) Synthesis and solution properties of temperature-sensitive copolymers based on NIPAM. J Appl Polym Sci 116:1099–1105

    Article  CAS  Google Scholar 

  6. Lu W, Zhao B, Li N, Yao Y, Chen W (2010) Thermosensitive copolymer with cobalt phthalocyanine and catalytic behavior based on adjustable LCST. React Func Polym 70:135–141

    Article  CAS  Google Scholar 

  7. Li Z, Guan J (2011) Thermosensitive hydrogels for drug delivery. Expert Opin Drug Deliv 8:991–1007

    Article  CAS  Google Scholar 

  8. Huynh CT, Nguyen MK, Lee DS (2011) Injectable block copolymer hydrogels: achievements and future challenges for biomedical applications. Macromolecules 44:6629–6636

    Article  CAS  Google Scholar 

  9. Buenger D, Topuz F, Groll J (2012) Hydrogels in sensing applications. Prog Polym Sci 37:1678–1719

    Article  CAS  Google Scholar 

  10. Toh WS, Loh XJ (2014) Advances in hydrogel delivery systems for tissue engineering. Mater Sci Eng C 45:690–697

    Article  CAS  Google Scholar 

  11. Overstreet DJ, Dutta D, Stabenfeldt SE, Vernon BL (2012) Injectable hydrogels. J Polym Sci Part B: Polym Phys 50:881–903

    Article  CAS  Google Scholar 

  12. Ko DY, Shinde UP, Yeon B, Jeong B (2013) Recent progress of in situ formed gels for biomedical applications. Prog Polym Sci 38:672–701

    Article  CAS  Google Scholar 

  13. Yang JA, Yeom J, Hwang BW, Hoffman AS, Hahn SK (2014) In situ-forming injectable hydrogels for regenerative medicine. Prog Polym Sci 39:1973–1986

    Article  CAS  Google Scholar 

  14. Singh NK, Lee DS (2014) In situ gelling pH- and temperature-sensitive biodegradable block copolymer hydrogels for drug delivery. J Control Release 193:214–227

    Article  CAS  Google Scholar 

  15. Schild HG (1992) Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci 17:163–249

    Article  CAS  Google Scholar 

  16. Lutz JF, Akdemir O, Hoth A (2006) Point by point comparison of two thermosensitive polymers exhibiting similar LCST: is the age of poly(NIPAM) over? J Am Chem Soc 128:13046–13047

    Article  CAS  Google Scholar 

  17. Neradovic DJ, Hinrichs WL, van den Bosch JJ K, Hennink WE (1999) Poly(N-isopropylacrylamide) with hydrolyzable lactic acid ester side groups: a new type of thermosensitive polymer. Macromol Rapid Commun 20:577–581

    Article  CAS  Google Scholar 

  18. Lee BH, Vernon B (2005) Copolymers of N-isopropylacrylamide, HEMA-lactate and acrylic acid with time dependent lower critical solution temperature as a bioresorbable carrier. Polym Int 54:418–422

    Article  CAS  Google Scholar 

  19. Lee BH, Vernon B (2005) In situ-gelling, erodible N-isopropylacrylamide copolymers. Macromol Biosci 5:629–635

    Article  CAS  Google Scholar 

  20. Guan J, Hong Y, Ma Z, Wagner WR (2008) Protein-reactive, thermoresponsive copolymers with high flexibility and biodegradability. Biomacromolecules 9:1283–1292

    Article  CAS  Google Scholar 

  21. Wang F, Li Z, Khan M, Tamama K, Kuppusamy P, Wagner WR, Sen CK, Guan J (2010) Injectable, rapid gelling and highly flexible hydrogel composites as growth factor and cell carriers. Acta Biomater 6:1978–1991

    Article  CAS  Google Scholar 

  22. Cui Z, Lee BH, Pauken C, Vernon BL (2011) Degradation, cytotoxicity, and biocompatibility of NIPAAm-based thermosensitive, injectable, and bioresorbable polymer hydrogels. J Biomed Mat Res 98A:159–166

    Article  CAS  Google Scholar 

  23. Sun LF, Zhuo RX, Liu ZL (2003) Studies on the synthesis and properties of temperature responsive and biodegradable hydrogels. Macromol Biosci 3:725–728

    Article  CAS  Google Scholar 

  24. Ren L, Agarwal S (2007) Synthesis, characterization and properties evaluation of poly[(N-isopropylacrylamide)-co-ester]s. Macromol Chem Phys 208:245–253

    Article  CAS  Google Scholar 

  25. Galperin A, Long TJ, Ratner BD (2010) Degradable, thermosensitive poly(N-isopropylacrylamide)-based scaffolds with controlled porosity for tissue engineering applications. Biomacromolecules 11:2583–2592

    Article  CAS  Google Scholar 

  26. 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 87:345–358

    Article  Google Scholar 

  27. Mizuntani M, Satoh K, Kamigaito M (2011) Degradable poly(N-isopropylacrylamide)with tunable thermosensitivity by simultaneous chain- and step-growth radical polymerization. Macromolecules 44:2382–2386

    Article  CAS  Google Scholar 

  28. Han CK, Bae YH (1998) Inverse thermally-reversible gelation of aqueous N-isopropylacrylamide copolymer solutions. Polymer 39:2809–2814

    Article  CAS  Google Scholar 

  29. Teodorescu M, Negru I, Stanescu PO, Draghici C, Lungu A, Sarbu A (2010) Thermogelation properties of poly(N-isopropylacrylamide)-block-poly(ethylene glycol)-block-poly(N-isopropylacrylamide) triblock copolymer aqueous solutions. React Func Polym 70:790–797

    Article  CAS  Google Scholar 

  30. Overstreet DJ, McLemore RY, Doan BD, Farag A, Vernon BL (2013) Temperature-responsive graft copolymer hydrogels for controlled swelling and drug delivery. Soft Materials 11:294–304

    Article  CAS  Google Scholar 

  31. Shim MS, Lee HT, Shim WS, Park I, Lee H, Chang T, Kim SW, Lee DS (2002) Poly(D, L-Lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D, L-lactic acid-co-glycolic acid) triblock copolymer and thermoreversible phase transition in water. J Biomed Mater Res 61:188–196

    Article  CAS  Google Scholar 

  32. Taktak FF, Bütün V (2010) Synthesis and physical gels of pH- and thermo-responsive tertiary amine methacrylate based ABA triblock copolymers and drug release studies. Polymer 51:3618–3626

    Article  CAS  Google Scholar 

  33. De Graaf AJ, Boere KWM, Kemmink J, Fokkink RG, Van Nostrum CF, Rijkers DTS, Van der Gucht J, Wienk H, Baldus M, Mastrobattista E, Vermonden T, Hennink WE (2011) Looped structure of flowerlike micelles revealed by 1H NMR relaxometry and light scattering. Langmuir 27:9843–9848

    Article  Google Scholar 

  34. Chassenieux C, Nicolai T, Benyahia L (2011) Rheology of associative polymer solutions. Curr Opin Colloid Interface Sci 16:18–26

    Article  CAS  Google Scholar 

  35. Wickel H, Agarwal S (2003) Synthesis and characterization of copolymers of 5,6-benzo-2-methylene-1,3-dioxepane and styrene. Macromolecules 36:6152–6159

    Article  CAS  Google Scholar 

  36. You YZ, Oupicky D (2007) Synthesis of temperature-responsive heterobifunctional block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide). Biomacromolecules 8:98–105

    Article  CAS  Google Scholar 

  37. Lu F, Luo Y, Li B, Zhao Q, Schork FJ (2010) Synthesis of thermosensitive nano-capsules via inverse miniemulsion polymerization using PEO-RAFT agent. Macromolecules 43:568–571

    Article  CAS  Google Scholar 

  38. 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 1:953–964

    Article  CAS  Google Scholar 

  39. Bailey WJ, Ni Z, Wu SR (1982) Free radical ring-opening polymerization of 4,7-dimethyl-2-methylene-1,3-dioxepane and 5,6-benzo-2-methylene-1,3-dioxepane. Macromolecules 15:711–714

    Article  CAS  Google Scholar 

  40. 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 46:11698–11706

    Article  CAS  Google Scholar 

  41. Lutz JF, Andrieu J, Uzgun S, Rudolph C, Agarwal S (2007) Biocompatible, thermoresponsive, and biodegradable: simple preparation of “all-in-one” biorelevant polymers. Macromolecules 40:8540–8543

    Article  CAS  Google Scholar 

  42. Zhang Y, Zheng M, Kissel T, Agarwal S (2012) Design and biophysical characterization of bioresponsive degradable poly(dimethylaminoethyl methacrylate) based polymers for in vitro DNA transfection. Biomacromolecules 13:313–322

    Article  CAS  Google Scholar 

  43. 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 52:1633–1641

    Article  CAS  Google Scholar 

  44. Gomez d’Ayala G, Malinconico M, Laurienzo P, Taedy 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 52:104–111

    Google Scholar 

  45. Odian G (2004) Principles of polymerization, Fourthth edn. J. Wiley and Sons, Hoboken, New Jersey

    Book  Google Scholar 

  46. Stanescu PO, Cursaru B, Teodorescu M (2009) Thermal properties of networks prepared from α, ω-diepoxy terminated poly(ethylene glycol)s and aliphatic polyamines. Mater Plast 46:419–425

    CAS  Google Scholar 

  47. Negru I, Teodorescu M, Stanescu PO, Draghici C, Lungu A, Sarbu A (2013) Thermogelation properties of ABA triblock copolymers of poly(ethylene glycol) (B) and copolyacrylates of oligo(ethylene glycol)s (A) in aqueous solution. Soft Materials 11:149–156

    Article  CAS  Google Scholar 

  48. 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 52:193–197

    Google Scholar 

  49. Moad G, Rizzardo E, Thang SH (2011) End-functional polymers, thiocarbonylthio group removal/transformation and reversible addition-fragmentation-chain transfer (RAFT) polymerization. Polym Int 60:9–25

    Article  CAS  Google Scholar 

  50. Zhang Y, Furyk S, Bergbreiter DE, Cremer PS (2005) Specific ion effects on the water solubility of macromolecules: PNIPAM and the Hohmeister series. J Am Chem Soc 127:14505–14510

    Article  CAS  Google Scholar 

  51. Xia Y, Yin X, Burke NAD, Stöver HDH (2005) Thermal response of narrow-disperse poly(N-isopropylacrylamide) prepared by atom transfer radical polymerization. Macromolecules 38:5937–5943

    Article  CAS  Google Scholar 

  52. Patel T, Ghosh G, Yusa S, Bahadur P (2011) Solution behavior of poly(N-isopropylacrylamide) in water: effect of additives. J Disp Sci Technol 32:1111–1118

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by a grant of the Ministry of National Education, CNCS–UEFISCDI, project number PN-II-ID-PCE-2012-4-0082.

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Authors and Affiliations

  1. Department of Bioresources and Polymer Science, Faculty of Applied Chemistry and Materials Science, Polytechnic University of Bucharest, 1-7 Gh. Polizu Street, 011061, Bucharest, Romania

    Gabriel Turturicǎ, Maria Andrei, Paul O. Stǎnescu & Mircea Teodorescu

  2. Center of Organic Chemistry of the Romanian Academy, 202B Splaiul Independentei, 060023, Bucharest, Romania

    Constantin Drǎghici & Dumitru Mircea Vuluga

  3. National Institute of Research and Development for Chemistry and Petrochemistry—ICECHIM, 202 Splaiul Independentei, 060021, Bucharest, Romania

    Anamaria Zaharia & Andrei Sârbu

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  1. Gabriel Turturicǎ
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Turturicǎ, G., Andrei, M., Stǎnescu, P.O. et al. 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, 743–753 (2016). https://doi.org/10.1007/s00396-016-3831-9

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