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Recent Advances in Polymer-Cyclodextrin Inclusion Complex-Based Supramolecular Hydrogel for Biomedical Applications

  • Xia Song
  • Jun LiEmail author
Chapter
Part of the Springer Series in Biomaterials Science and Engineering book series (SSBSE, volume 12)

Abstract

The supramolecular self-assembly formed between cyclodextrins (CDs) and polymers has inspired interesting development of many novel supramolecular hydrogels as injectable delivery systems for sustained drug or gene release due to their thixotropic nature, thermoreversible properties, and biocompatibility. A large number of supramolecular hydrogels have been formed between CDs and poly(ethylene oxide) or its block copolymers with a hydrophobic segment. The intermolecular interactions by the hydrophobic blocks further strengthen and stabilize the supramolecular network, opening up a new approach for designing long-term sustained delivery systems. Recent advances in this field have greatly improved the rheological and delivery properties of the supramolecular hydrogels, making them more suitable for biomedical applications. Novel supramolecular structures based on pseudoblock copolymers formed by host-guest inclusion complexation with new stimuli-responsive properties have also been developed, forming “smart” supramolecular hydrogels with more desired and promising properties for controlled release applications.

Keywords

Polymer Cyclodextrin Inclusion complex Hydrogel Drug delivery Gene delivery 

References

  1. 1.
    Lehn JM (1995) Supramolecular chemistry: concepts and perspectives. VCH Verlagsgesellschaft mbH.  https://doi.org/10.1002/3527607439 CrossRefGoogle Scholar
  2. 2.
    Nepogodiev SA, Stoddart JF (1998) Cyclodextrin-based catenanes and rotaxanes. Chem Rev 98(5):1959–1976.  https://doi.org/10.1021/cr970049w CrossRefGoogle Scholar
  3. 3.
    Raymo FM, Stoddart JF (1999) Interlocked macromolecules. Chem Rev 99(7):1643–1664.  https://doi.org/10.1021/cr970081q CrossRefGoogle Scholar
  4. 4.
    Ashton PR, Ballardini R, Balzani V, Bělohradský M, Gandolfi MT, Philp D, Prodi L, Raymo FM, Reddington MV, Spencer N, Stoddart JF, Venturi M, Williams DJ (1996) Self-assembly, spectroscopic, and electrochemical properties of [n]rotaxanes1. J Am Chem Soc 118(21):4931–4951.  https://doi.org/10.1021/ja954334d CrossRefGoogle Scholar
  5. 5.
    Chichak KS, Cantrill SJ, Pease AR, Chiu S-H, Cave GWV, Atwood JL, Stoddart JF (2004) Molecular borromean rings. Science 304(5675):1308–1312CrossRefGoogle Scholar
  6. 6.
    Schmieder R, Hübner G, Seel C, Vögtle F (1999) The first cyclodiasteromeric [3]rotaxane. Angew Chem Int Ed 38(23):3528–3530.  https://doi.org/10.1002/(SICI)1521-3773(19991203)38:23<3528::AID-ANIE3528>3.0.CO;2-N CrossRefGoogle Scholar
  7. 7.
    Vögtle F, Dünnwald T, Schmidt T (1996) Catenanes and rotaxanes of the amide type. Acc Chem Res 29(9):451–460.  https://doi.org/10.1021/ar950200t CrossRefGoogle Scholar
  8. 8.
    Gibson HW, Bheda MC, Engen PT (1994) Rotaxanes, catenanes, polyrotaxanes, polycatenanes and related materials. Prog Polym Sci 19(5):843–945.  https://doi.org/10.1016/0079-6700(94)90034-5 CrossRefGoogle Scholar
  9. 9.
    Harada A, Li J, Kamachi M (1992) The molecular necklace: a rotaxane containing many threaded [alpha]-cyclodextrins. Nature 356(6367):325–327CrossRefGoogle Scholar
  10. 10.
    Li J, Loh XJ (2008) Cyclodextrin-based supramolecular architectures: syntheses, structures, and applications for drug and gene delivery. Adv Drug Deliv Rev 60(9):1000–1017.  https://doi.org/10.1016/j.addr.2008.02.011 CrossRefGoogle Scholar
  11. 11.
    Bender ML, Komiyama M (1978) Cyclodextrin chemistry. Reactivity and structure: concepts in organic chemistry, vol 6. Springer-Verlag, Berlin/Heidelberg.  https://doi.org/10.1007/978-3-642-66842-5 CrossRefGoogle Scholar
  12. 12.
    Szejtli J (1998) Introduction and general overview of cyclodextrin chemistry. Chem Rev 98(5):1743–1754.  https://doi.org/10.1021/cr970022c CrossRefGoogle Scholar
  13. 13.
    Wenz G, Han B-H, Müller A (2006) Cyclodextrin rotaxanes and polyrotaxanes. Chem Rev 106(3):782–817.  https://doi.org/10.1021/cr970027+ CrossRefGoogle Scholar
  14. 14.
    Chen Y, Liu Y (2010) Cyclodextrin-based bioactive supramolecular assemblies. Chem Soc Rev 39(2):495–505.  https://doi.org/10.1039/B816354P CrossRefGoogle Scholar
  15. 15.
    Peppas NA (1987) Hydrogels in medicine and pharmacy, vol 1. CRC Press Inc., Boca RatonGoogle Scholar
  16. 16.
    Park K, Shalaby WSW, Park H (1993) Biodegradable hydrogels for drug delivery. Technomic Publishing Company Inc., LancasterGoogle Scholar
  17. 17.
    Kishida A, Ikada Y (2002) In: Dumitriu S (ed) Polymeric biomaterials. New York, Marcel DekkerGoogle Scholar
  18. 18.
    Li J (2004) In: Teoh SH (ed) Biomaterials engineering and processing series, vol 1. World Scientific Publishing, HackensackGoogle Scholar
  19. 19.
    Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 54(1):3–12.  https://doi.org/10.1016/S0169-409X(01)00239-3 CrossRefGoogle Scholar
  20. 20.
    Kim SW, Bae YH, Okano T (1992) Hydrogels: swelling, drug loading, and release. Pharm Res 9(3):283–290.  https://doi.org/10.1023/a:1015887213431 CrossRefGoogle Scholar
  21. 21.
    Park H, Park K (1996) Biocompatibility issues of implantable drug delivery systems. Pharm Res 13(12):1770–1776.  https://doi.org/10.1023/a:1016012520276 CrossRefGoogle Scholar
  22. 22.
    Li J (2009) Cyclodextrin inclusion polymers forming hydrogels. In: Wenz G (ed) Inclusion polymers, Advances in polymer science, vol 222. Springer, Berlin Heidelberg, pp 175–203.  https://doi.org/10.1007/12_2008_9 CrossRefGoogle Scholar
  23. 23.
    Li J, Li X, Ni X, Wang X, Li H, Leong KW (2006) Self-assembled supramolecular hydrogels formed by biodegradable PEO–PHB–PEO triblock copolymers and α-cyclodextrin for controlled drug delivery. Biomaterials 27(22):4132–4140.  https://doi.org/10.1016/j.biomaterials.2006.03.025 CrossRefGoogle Scholar
  24. 24.
    Li J (2010) Self-assembled supramolecular hydrogels based on polymer–cyclodextrin inclusion complexes for drug delivery. NPG Asia Mater 2:112–118CrossRefGoogle Scholar
  25. 25.
    Liu KL, Zhang Z, Li J (2011) Supramolecular hydrogels based on cyclodextrin-polymer polypseudorotaxanes: materials design and hydrogel properties. Soft Matter 7(24):11290–11297CrossRefGoogle Scholar
  26. 26.
    Li JJ, Zhao F, Li J (2011) Polyrotaxanes for applications in life science and biotechnology. Appl Microbiol Biotechnol 90(2):427–443.  https://doi.org/10.1007/s00253-010-3037-x CrossRefGoogle Scholar
  27. 27.
    Li J, Zhao F, Li J (2011) Supramolecular polymers based on cyclodextrins for drug and gene delivery. In: Nyanhongo GS, Steiner W, Gübitz G (eds) Biofunctionalization of polymers and their applications, Advances in biochemical engineering/biotechnology, vol 125. Springer, Berlin/Heidelberg, pp 207–249.  https://doi.org/10.1007/10_2010_91 CrossRefGoogle Scholar
  28. 28.
    Li J, Harada A, Kamachi M (1994) Sol-gel transition during inclusion complex formation between [α]-cyclodextrin and high molecular weight poly(ethylene glycol)s in aqueous solution. Polym J 26(9):1019–1026.  https://doi.org/10.1295/polymj.26.1019 CrossRefGoogle Scholar
  29. 29.
    Li J, Ni X, Leong KW (2003) Injectable drug-delivery systems based on supramolecular hydrogels formed by poly(ethylene oxide)s and α-cyclodextrin. J Biomed Mater Res A 65A(2):196–202.  https://doi.org/10.1002/jbm.a.10444 CrossRefGoogle Scholar
  30. 30.
    Jeong B, Bae YH, Lee DS, Kim SW (1997) Biodegradable block copolymers as injectable drug-delivery systems. Nature 388(6645):860–862CrossRefGoogle Scholar
  31. 31.
    Jeong B, Bae YH, Kim SW (2000) Drug release from biodegradable injectable thermosensitive hydrogel of PEG–PLGA–PEG triblock copolymers. J Control Release 63(1–2):155–163.  https://doi.org/10.1016/S0168-3659(99)00194-7 CrossRefGoogle Scholar
  32. 32.
    Li J, Li X, Zhou Z, Ni X, Leong KW (2001) Formation of supramolecular hydrogels induced by inclusion complexation between pluronics and α-cyclodextrin. Macromolecules 34(21):7236–7237.  https://doi.org/10.1021/ma010742s CrossRefGoogle Scholar
  33. 33.
    Bromberg LE, Ron ES (1998) Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Adv Drug Deliv Rev 31(3):197–221.  https://doi.org/10.1016/S0169-409X(97)00121-X CrossRefGoogle Scholar
  34. 34.
    Loh XJ, Goh SH, Li J (2007) New biodegradable thermogelling copolymers having very low gelation concentrations. Biomacromolecules 8(2):585–593.  https://doi.org/10.1021/bm0607933 CrossRefGoogle Scholar
  35. 35.
    Ni X, Cheng A, Li J (2009) Supramolecular hydrogels based on self-assembly between PEO-PPO-PEO triblock copolymers and α-cyclodextrin. J Biomed Mater Res A 88A(4):1031–1036.  https://doi.org/10.1002/jbm.a.31906 CrossRefGoogle Scholar
  36. 36.
    Li J, Li X, Ni X, Leong KW (2003) Synthesis and characterization of new biodegradable amphiphilic poly(ethylene oxide)-b-poly[(R)-3-hydroxy butyrate]-b-poly(ethylene oxide) triblock copolymers. Macromolecules 36(8):2661–2667.  https://doi.org/10.1021/ma025725x CrossRefGoogle Scholar
  37. 37.
    Li X, Li J, Leong KW (2003) Preparation and characterization of inclusion complexes of biodegradable amphiphilic poly(ethylene oxide)−poly[(R)-3-hydroxybutyrate]−poly(ethylene oxide) triblock copolymers with cyclodextrins. Macromolecules 36(4):1209–1214.  https://doi.org/10.1021/ma0213347 CrossRefGoogle Scholar
  38. 38.
    Li X, Li J, Leong KW (2004) Role of intermolecular interaction between hydrophobic blocks in block-selected inclusion complexation of amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) triblock copolymers with cyclodextrins. Polymer 45(20):6845–6851.  https://doi.org/10.1016/j.polymer.2004.07.038 CrossRefGoogle Scholar
  39. 39.
    Li J, Ni X, Li X, Tan NK, Lim CT, Ramakrishna S, Leong KW (2005) Micellization phenomena of biodegradable amphiphilic triblock copolymers consisting of poly(β-hydroxyalkanoic acid) and poly(ethylene oxide). Langmuir 21(19):8681–8685.  https://doi.org/10.1021/la0515266 CrossRefGoogle Scholar
  40. 40.
    Liu KL, J-l Z, Li J (2010) Elucidating rheological property enhancements in supramolecular hydrogels of short poly[(R,S)-3-hydroxybutyrate]-based amphiphilic triblock copolymer and [small alpha]-cyclodextrin for injectable hydrogel applications. Soft Matter 6(10):2300–2311.  https://doi.org/10.1039/B923472A CrossRefGoogle Scholar
  41. 41.
    Liu KL, Goh SH, Li J (2008) Controlled synthesis and characterizations of amphiphilic poly[(R,S)-3-hydroxybutyrate]-poly(ethylene glycol)-poly[(R,S)-3-hydroxybutyrate] triblock copolymers. Polymer 49(3):732–741.  https://doi.org/10.1016/j.polymer.2007.12.017 CrossRefGoogle Scholar
  42. 42.
    Liu KL, Goh SH, Li J (2008) Threading α-cyclodextrin through poly[(R,S)-3-hydroxybutyrate] in poly[(R,S)-3-hydroxybutyrate]−poly(ethylene glycol)−poly[(R,S)-3-hydroxybutyrate] triblock copolymers: formation of block-selected polypseudorotaxanes. Macromolecules 41(16):6027–6034.  https://doi.org/10.1021/ma800366v CrossRefGoogle Scholar
  43. 43.
    Loh XJ, Sng KBC, Li J (2008) Synthesis and water-swelling of thermo-responsive poly(ester urethane)s containing poly(epsilon-caprolactone), poly(ethylene glycol) and poly(propylene glycol). Biomaterials 29(22):3185–3194.  https://doi.org/10.1016/j.biomaterials.2008.04.015 CrossRefGoogle Scholar
  44. 44.
    Wu D-Q, Wang T, Lu B, Xu X-D, Cheng S-X, Jiang X-J, Zhang X-Z, Zhuo R-X (2008) Fabrication of supramolecular hydrogels for drug delivery and stem cell encapsulation. Langmuir 24(18):10306–10312.  https://doi.org/10.1021/la8006876 CrossRefGoogle Scholar
  45. 45.
    Wang T, Jiang X-J, Lin T, Ren S, Li X-Y, Zhang X-Z, Q-z T (2009) The inhibition of postinfarct ventricle remodeling without polycythaemia following local sustained intramyocardial delivery of erythropoietin within a supramolecular hydrogel. Biomaterials 30(25):4161–4167.  https://doi.org/10.1016/j.biomaterials.2009.04.033 CrossRefGoogle Scholar
  46. 46.
    Zhang Z-X, Liu KL, Li J (2013) A thermoresponsive hydrogel formed from a star–star supramolecular architecture. Angew Chem Int Ed 52(24):6180–6184.  https://doi.org/10.1002/anie.201301956 CrossRefGoogle Scholar
  47. 47.
    Zhang Z-X, Liu X, Xu FJ, Loh XJ, Kang E-T, Neoh K-G, Li J (2008) Pseudo-block copolymer based on star-shaped poly(N-isopropylacrylamide) with a β-cyclodextrin core and guest-bearing PEG: controlling thermoresponsivity through supramolecular self-assembly. Macromolecules 41(16):5967–5970.  https://doi.org/10.1021/ma8009646 CrossRefGoogle Scholar
  48. 48.
    Zhang Z-X, Liu KL, Li J (2011) Self-assembly and micellization of a dual thermoresponsive supramolecular pseudo-block copolymer. Macromolecules 44(5):1182–1193.  https://doi.org/10.1021/ma102196q CrossRefGoogle Scholar
  49. 49.
    Song X, Wen Y, J-l Z, Zhao F, Zhang Z-X, Li J (2016) Thermoresponsive delivery of paclitaxel by β-cyclodextrin-based poly(N-isopropylacrylamide) star polymer via inclusion complexation. Biomacromolecules 17:3957–3963.  https://doi.org/10.1021/acs.biomac.6b01344 CrossRefGoogle Scholar
  50. 50.
    Song X, J-l Z, Wen Y, Zhao F, Zhang Z-X, Li J (2017) Thermoresponsive supramolecular micellar drug delivery system based on star-linear pseudo-block polymer consisting of β-cyclodextrin-poly(N-isopropylacrylamide) and adamantyl-poly(ethylene glycol). J Colloid Interface Sci 490:372–379.  https://doi.org/10.1016/j.jcis.2016.11.056 CrossRefGoogle Scholar
  51. 51.
    Schild HG (1992) Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci 17(2):163–249.  https://doi.org/10.1016/0079-6700(92)90023-R CrossRefGoogle Scholar
  52. 52.
    Sandier A, Brown W, Mays H, Amiel C (2000) Interaction between an adamantane end-capped poly(ethylene oxide) and a β-cyclodextrin polymer. Langmuir 16(4):1634–1642.  https://doi.org/10.1021/la990873a CrossRefGoogle Scholar
  53. 53.
    Auzély-Velty R, Rinaudo M (2002) New supramolecular assemblies of a cyclodextrin-grafted chitosan through specific complexation. Macromolecules 35(21):7955–7962.  https://doi.org/10.1021/ma020664o CrossRefGoogle Scholar
  54. 54.
    Kretschmann O, Choi SW, Miyauchi M, Tomatsu I, Harada A, Ritter H (2006) Switchable hydrogels obtained by supramolecular cross-linking of adamantyl-containing LCST copolymers with cyclodextrin dimers. Angew Chem Int Ed 45(26):4361–4365.  https://doi.org/10.1002/anie.200504539 CrossRefGoogle Scholar
  55. 55.
    Charlot A, Auzély-Velty R, Rinaudo M (2003) Specific interactions in model charged polysaccharide systems†. J Phys Chem B 107(32):8248–8254.  https://doi.org/10.1021/jp022580n CrossRefGoogle Scholar
  56. 56.
    Charlot A, Auzély-Velty R (2007) Synthesis of novel supramolecular assemblies based on hyaluronic acid derivatives bearing bivalent β-Cyclodextrin and adamantane moieties. Macromolecules 40(4):1147–1158.  https://doi.org/10.1021/ma062322e CrossRefGoogle Scholar
  57. 57.
    Koopmans C, Ritter H (2008) Formation of physical hydrogels via host−guest interactions of β-cyclodextrin polymers and copolymers bearing adamantyl groups. Macromolecules 41(20):7418–7422.  https://doi.org/10.1021/ma801202f CrossRefGoogle Scholar
  58. 58.
    Li Z, Yin H, Zhang Z, Liu KL, Li J (2012) Supramolecular anchoring of DNA polyplexes in cyclodextrin-based polypseudorotaxane hydrogels for sustained gene delivery. Biomacromolecules 13(10):3162–3172.  https://doi.org/10.1021/bm300936x CrossRefGoogle Scholar
  59. 59.
    Agarwal A, Unfer RC, Mallapragada SK (2008) Dual-role self-assembling nanoplexes for efficient gene transfection and sustained gene delivery. Biomaterials 29(5):607–617.  https://doi.org/10.1016/j.biomaterials.2007.10.010 CrossRefGoogle Scholar
  60. 60.
    Deng J, Luo Y, Zhang L-M (2011) PEGylated polyamidoamine dendron-assisted encapsulation of plasmid DNA into in situ forming supramolecular hydrogel. Soft Matter 7(13):5944–5947.  https://doi.org/10.1039/C1SM05259D CrossRefGoogle Scholar
  61. 61.
    Ma D, Zhang H-B, Chen D-H, Zhang L-M (2011) Novel supramolecular gelation route to in situ entrapment and sustained delivery of plasmid DNA. J Colloid Interface Sci 364(2):566–573.  https://doi.org/10.1016/j.jcis.2011.08.051 CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Biomedical Engineering, Faculty of EngineeringNational University of SingaporeSingaporeSingapore

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