Skip to main content
SpringerLink
Log in

Injectable micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs

  • Delivery Systems
  • Original Research
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

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

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2012;64:18–23.

    Article  Google Scholar 

  2. Yu L, Ding J. Injectable hydrogels as unique biomedical materials. Chem Soc Rev. 2008;37:1473–81.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  4. Chen G, Jiang M. Cyclodextrin-based inclusion complexation bridging supramolecular chemistry and macromolecular self-assembly. Chem Soc Rev. 2011;40:2254–66.

    Article  Google Scholar 

  5. Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev. 2012;64:49–60.

    Article  Google Scholar 

  6. Yan X, Wang F, Zheng B, Huang F. Stimuli-responsive supramolecular polymeric materials. Chem Soc Rev. 2012;41:6042–65.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  12. Appel EA, del Barrio J, Loh XJ, Scherman OA. Supramolecular polymeric hydrogels. Chem Soc Rev. 2012;41:6195–214.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

Download references

Acknowledgments

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).

Author information

Authors and Affiliations

  1. Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People’s Republic of China

    CuiXiang Fu, XiaoXiao Lin, Jun Wang, ZhengFeng Lin & GuangYong Lin

  2. Department of Laboratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People’s Republic of China

    XiaoQun Zheng

  3. Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People’s Republic of China

    XingYi Li

Authors
  1. CuiXiang Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. XiaoXiao Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. XiaoQun Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. XingYi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. ZhengFeng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. GuangYong Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to GuangYong Lin.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (MOV 27293 kb)

Supplementary material 2 (DOCX 1963 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, C., Lin, X., Wang, J. et al. Injectable micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs. J Mater Sci: Mater Med 27, 73 (2016). https://doi.org/10.1007/s10856-016-5682-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-016-5682-9

Keywords

Search

Navigation