Injectable micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs

  • CuiXiang Fu
  • XiaoXiao Lin
  • Jun Wang
  • XiaoQun Zheng
  • XingYi Li
  • ZhengFeng Lin
  • GuangYong LinEmail author
Delivery Systems Original Research
Part of the following topical collections:
  1. Delivery Systems


In this paper, an injectable micellar supramolecular hydrogel composed of α-cyclodextrin (α-CD) and monomethoxy poly(ethylene glycol)-b-poly(ε-caplactone) (MPEG5000-PCL5000) micelles was developed by a simple method for hydrophobic anticancer drug delivery. By mixing α-CD aqueous solution and MPEG5000-PCL5000 micelles, an injectable micellar supramolecular hydrogel could be formed under mild condition due to the inclusion complexation between α-CD and MPEG segment of MPEG5000-PCL5000 micelles. The resultant supramolecular hydrogel was thereafter characterized by X-ray diffraction (XRD) and Scanning electron microscopy (SEM). The effect of α-CD amount on the gelation time, mechanical strength and thixotropic property was studied by a rheometer. Payload of hydrophobic paclitaxel (PTX) to supramolecular hydrogel was achieved by encapsulation of PTX into MPEG5000-PCL5000 micelles prior mixing with α-CD aqueous solution. In vitro release study showed that the release behavior of PTX from hydrogel could be modulated by change the α-CD amount in hydrogel. Furthermore, such supramolecular hydrogel could enhance the biological activity of encapsulated PTX compared to free PTX, as indicated by in vitro cytotoxicity assay. All these results indicated that the developed micellar supramolecular hydrogel might be a promising injectable drug delivery system for anticancer therapy.

Graphical Abstract


Gelation Time Hydrophobic Drug Hydrogel Sample Control Drug Delivery System Supramolecular Hydrogel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thanks to the synthesis of MPEG5000-PCL5000 block polymer by Li XY. The authors acknowledge the financial support from Zhejiang Medicines Health Science and Technology Program (2012KYB132).

Supplementary material

Supplementary material 1 (MOV 27293 kb)

10856_2016_5682_MOESM2_ESM.docx (1.9 mb)
Supplementary material 2 (DOCX 1963 kb)


  1. 1.
    Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2012;64:18–23.CrossRefGoogle Scholar
  2. 2.
    Yu L, Ding J. Injectable hydrogels as unique biomedical materials. Chem Soc Rev. 2008;37:1473–81.CrossRefGoogle Scholar
  3. 3.
    Singh NK, Lee DS. In situ gelling pH-and temperature-sensitive biodegradable block copolymer hydrogels for drug delivery. J Control Release. 2014;193:214–27.CrossRefGoogle Scholar
  4. 4.
    Chen G, Jiang M. Cyclodextrin-based inclusion complexation bridging supramolecular chemistry and macromolecular self-assembly. Chem Soc Rev. 2011;40:2254–66.CrossRefGoogle Scholar
  5. 5.
    Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev. 2012;64:49–60.CrossRefGoogle Scholar
  6. 6.
    Yan X, Wang F, Zheng B, Huang F. Stimuli-responsive supramolecular polymeric materials. Chem Soc Rev. 2012;41:6042–65.CrossRefGoogle Scholar
  7. 7.
    Ma H, He C, Cheng Y, Li D, Gong Y, Liu J, Tian H, Chen X. PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for osteosarcoma treatment. Biomaterials. 2014;35:8723–34.CrossRefGoogle Scholar
  8. 8.
    Yu L, Zhang Z, Ding J. Influence of LA and GA sequence in the PLGA block on the properties of thermogelling PLGA-PEG-PLGA block copolymers. Biomacromolecules. 2011;12:1290–7.CrossRefGoogle Scholar
  9. 9.
    Ni P, Ding Q, Fan M, Liao J, Qian Z, Luo J, Li X, Luo F, Yang Z, Wei Y. Injectable thermosensitive PEG-PCL-PEG hydrogel/acellular bone matrix composite for bone regeneration in cranial defects. Biomaterials. 2014;35:236–48.CrossRefGoogle Scholar
  10. 10.
    Fu S, Ni P, Wang B, Chu B, Zheng L, Luo F, Luo J, Qian Z. Injectable and thermo-sensitive PEG-PCL-PEG copolymer/collagen/n-HA hydrogel composite for guided bone regeneration. Biomaterials. 2012;33:4801–9.CrossRefGoogle Scholar
  11. 11.
    Lin N, Dufresne A. Supramolecular hydrogels from in situ host-guest inclusion between chemically modified cellulose nanocrystals and cyclodextrin. Biomacromolecules. 2013;14:871–80.CrossRefGoogle Scholar
  12. 12.
    Appel EA, del Barrio J, Loh XJ, Scherman OA. Supramolecular polymeric hydrogels. Chem Soc Rev. 2012;41:6195–214.CrossRefGoogle Scholar
  13. 13.
    Zhang J, Ma PX. Cyclodextrin-based supramolecular systems for drug delivery: recent progress and future perspective. Adv Drug Deliv Rev. 2013;65:1215–33.CrossRefGoogle Scholar
  14. 14.
    Schmidt BVKJ, Hetzer M, Ritter H, Barner-Kowollik C. Complex macromolecular architecture design via cyclodextrin host/guest complexes. Prog Polym Sci. 2014;39:235–49.CrossRefGoogle Scholar
  15. 15.
    Li J, Li X, Ni X, Wang X, Li H, Leong KW. Self-assembled supramolecular hydrogels formed by biodegradable PEO-PHB-PEO triblock copolymers and α-cyclodextrin for controlled drug delivery. Biomaterials. 2006;27:4132–40.CrossRefGoogle Scholar
  16. 16.
    Zhang ZX, Liu KL, Li J. A thermoresponsive hydrogel formed from a star-star supramolecular architecture. Angew Chem Int Ed. 2013;125:6300–4.CrossRefGoogle Scholar
  17. 17.
    Yu J, Ha W, Sun J-N, Shi Y-P. Supramolecular hybrid hydrogel based on host-guest interaction and its application in drug delivery. ACS Appl Mater Inter. 2014;6:19544–51.CrossRefGoogle Scholar
  18. 18.
    Li X, Kong X, Shi S, Wang X, Guo G, Luo F, Zhao X, Wei Y, Qian Z. Physical, mechanical and biological properties of poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone)(CEC)/chitosan composite film. Carbohyd Polym. 2010;82:904–12.CrossRefGoogle Scholar
  19. 19.
    Li X, Zhang Z, Li J, Sun S, Weng Y, Chen H. Diclofenac/biodegradable polymer micelles for ocular applications. Nanoscale. 2012;4:4667–73.CrossRefGoogle Scholar
  20. 20.
    Zhu W, Li Y, Liu L, Chen Y, Wang C, Xi F. Supramolecular hydrogels from cisplatin-loaded block copolymer nanoparticles and β-cyclodextrins with a stepwise delivery property. Biomacromolecules. 2010;11:3086–92.CrossRefGoogle Scholar
  21. 21.
    Liu KL, Zhu J-l, Li J. Elucidating rheological property enhancements in supramolecular hydrogels of short poly [(R, S)-3-hydroxybutyrate]-based amphiphilic triblock copolymer and ɛ-cyclodextrin for injectable hydrogel applications. Soft Matter. 2010;6:2300–11.CrossRefGoogle Scholar
  22. 22.
    Khodaverdi E, Aboumaashzadeh M, Tekie FSM, Hadizadeh F, Tabassi SAS, Mohajeri SA, Khashyarmanesh Z, Haghighi HM. Sustained drug release using supramolecular hydrogels composed of cyclodextrin inclusion complexes with PCL/PEG multiple block copolymers. Iran Polym J. 2014;23:707–16.CrossRefGoogle Scholar
  23. 23.
    Zhao S-P, Zhang L-M, Ma D. Supramolecular hydrogels induced rapidly by inclusion complexation of poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) block copolymers with α-cyclodextrin in aqueous solutions. J Phys Chem B. 2006;110:12225–9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • CuiXiang Fu
    • 1
  • XiaoXiao Lin
    • 1
  • Jun Wang
    • 1
  • XiaoQun Zheng
    • 2
  • XingYi Li
    • 3
  • ZhengFeng Lin
    • 1
  • GuangYong Lin
    • 1
    Email author
  1. 1.Department of PharmacyThe Second Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China
  2. 2.Department of Laboratory MedicineThe Second Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China
  3. 3.Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospitalWenzhou Medical UniversityWenzhouPeople’s Republic of China

Personalised recommendations