Skip to main content
Log in

Biodegradable amphiphilic block-graft copolymers based on methoxy poly(ethylene glycol)-b-(polycarbonates-g-polycarbonates) for controlled release of doxorubicin

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

In this paper, novel biodegradable amphiphilic block-graft copolymers based on methoxy poly(ethylene glycol)-b-(polycarbonates-g-polycarbonates) (mPEG-b-(PATMC-g-PATMC)) were synthesized successfully for controlled release of doxorubicin (DOX). Backbone block copolymer, methoxy poly(ethylene glycol)-b-poly(5-allyloxy-1,3-dioxan-2-one) (mPEG-b-PATMC) was synthesized in bulk catalyzed by immobilized porcine pancreas lipase (IPPL). Then, mPEG-b-PATMC-O, the allyl epoxidation product of mPEG-b-PATMC, was further grafted by PATMC itself also using IPPL as the catalyst. The copolymers were characterized by 1N HMR and gel permeation chromatography results showed narrow molecular weight distributions. Stable micelle solutions could be prepared by dialysis method, while a monomodal and narrow size distribution could be obtained. Transmission electron microscopy (TEM) observation showed the micelles dispersed in spherical shape with nano-size before and after DOX loading. Compared with the block copolymers, the grafted structure could enhance the interaction of polymer chains with drug molecules and improve the drug-loading capacity and entrapment efficiency. Furthermore, the amphiphilic block-graft copolymers mPEG-b-(PATMC-g-PATMC) had low cytotoxicity and more sustained drug release behavior.

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

Access this article

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

Instant access to the full article PDF.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Park JH, Lee S, Kim JH, Park K, Kim K, Kwon IC. Polymeric nanomedicine for cancer therapy. Prog Polym Sci. 2008;33(1):113–7.

    Article  Google Scholar 

  2. Gemma V, Judit TP, Fernando F. Polymers and drug delivery systems. Curr Drug Deliv. 2012;9(4):367–94.

    Article  Google Scholar 

  3. McKee MG, Unal S, Wilkes GL, Long TE. Branched polyesters: recent advances in synthesis and performance. Prog Polym Sci. 2005;30(5):507–39.

    Article  Google Scholar 

  4. Zhang XJ, Chen FJ, Zhong ZL, Zhuo RX. Amphiphilic block-graft copolymers with a degradable backbone and polyethylene glycol pendant chains prepared via ring-opening polymerization of a macromonomer. Macromol Rapid Commun. 2010;31(24):2155–9.

    Article  Google Scholar 

  5. Riess G. Micellization of block copolymers. Prog Polym Sci. 2003;28(7):1107–70.

    Article  Google Scholar 

  6. Torchilin V. Tumor delivery of macromolecular drugs based on the EPR effect. Adv Drug Deliv Rev. 2011;63(3):131–5.

    Article  Google Scholar 

  7. Lee JH, Lee HB, Andrade JD. Blood compatibility of polyethylene oxide surfaces. Prog Polym Sci. 1995;20(6):1043–79.

    Article  Google Scholar 

  8. Molineux G. Pegylation: engineering improved pharmaceuticals for enhanced therapy. Cancer Treat Rev. 2002;28:13–6.

    Article  Google Scholar 

  9. Otsuka H, Nagasaki Y, Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev. 2003;55(3):403–19.

    Article  Google Scholar 

  10. Wang P, Tan KL, Kang ET. Surface modification of poly(tetrafluoroethylene) films via grafting of poly(ethylene glycol) for reduction in protein adsorption. J Biomater Sci Polym Ed. 2000;11(2):169–86.

    Article  Google Scholar 

  11. Essa S, Rabanel JM, Hildgen P. Effect of aqueous solubility of grafted moiety on the physicochemical properties of poly(d, l-lactide) (PLA) based nanoparticles. Int J Pharm. 2010;388(1–2):263–73.

    Article  Google Scholar 

  12. Qiu F, Feng J, Wu DQ, Zhang XZ, Zhuo RX. Nanosized micelles self-assembled from amphiphilic dextran-graft-methoxypolyethylene glycol/poly(ε-caprolactone) copolymers. Eur Polym J. 2009;45(4):1024–31.

    Article  Google Scholar 

  13. Zhang XJ, Zhang ZG, Zhong ZL, Zhuo RX. Amphiphilic block-graft copolymers poly(ethylene glycol)-b-(polycarbonates-g-palmitate) prepared via the combination of ring-opening polymerization and click chemistry. J Polym Sci Part A. 2012;50(13):2687–96.

    Article  Google Scholar 

  14. Feng J, Zhuo RX, Zhang XZ. Construction of functional aliphatic polycarbonates for biomedical applications. Prog Polym Sci. 2012;37(2):211–36.

    Article  Google Scholar 

  15. Zheng XM, Jiang T, He F. Synthesis and characterization of PNIPAM-b-polycarbonate copolymers as self-assembled thermosensitive micelles for drug delivery. Acta Polym Sinica. 2011;8:895–902.

    Article  Google Scholar 

  16. Zhang XJ, Mei HJ, Hu C, Zhong ZL, Zhuo RX. Amphiphilic triblock copolycarbonates with poly(glycerol carbonate) as hydrophilic blocks. Macromolecules. 2009;42(4):1010–6.

    Article  Google Scholar 

  17. Zhang Z, Grijpma DW, Feijen J. Thermo-sensitive transition of monomethoxy poly(ethylene glycol)-block-poly(trimethylene carbonate) films to micellar-like nanoparticles. J Control Release. 2006;112(1):57–63.

    Article  Google Scholar 

  18. Albertsson AC, Srivastava RK. Recent developments in enzyme-catalyzed ring-opening polymerization. Adv Drug Deliv Rev. 2008;60(9):1077–93.

    Article  Google Scholar 

  19. Kadokawa JI, Kobayashi S. Polymer synthesis by enzymatic catalysis. Curr Opin Chem Biol. 2010;14(2):145–53.

    Article  Google Scholar 

  20. Kobayashi S, Makinl A. Enzymatic polymer synthesis: an opportunity for green polymer chemistry. Chem Rev. 2009;109(11):5288–353.

    Article  Google Scholar 

  21. He F, Wang YX, Feng J, Zhuo RX, Wang XL. Synthesis of poly[(5-benzyloxy-trimethylene carbonate)-co-(5,5-dimethyl-1,3-dioxan-2-one)] catalyzed by immoblized lipase on silica particles with different size. Polymer. 2003;44(11):3215–9.

    Article  Google Scholar 

  22. Wang CF, Lin YX, Jiang T, He F. Zhuo RX Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery. Biomaterials. 2009;30(27):4824–32.

    Article  Google Scholar 

  23. He F, Wang CF, Jiang T, Han B. zhuo RX. Poly[(5-methyl-5-allyloxycarbonyl-trimethylene carbonate)-co-(5,5-dimethyl-trimethylene carbonate)] with grafted polyethylenimine as biodegradable polycations for efficient gene delivery. Biomacromolecules. 2010;11(11):3028–35.

    Article  Google Scholar 

  24. He F, Wang YP, Liu G, Jia HL, Feng J, Zhuo RX. Synthesis, characterization and ring-opening polymerization of a novel six-membered cyclic carbonate bearing pendent allyl ether group. Polymer. 2008;49(5):1185–90.

    Article  Google Scholar 

  25. Danquah MK, Zhang XA, Mahato RI. Extravasation of polymeric nanomedicines across tumor vasculature. Adv Drug Deliv Rev. 2011;63(8):623–39.

    Article  Google Scholar 

  26. Carstens MG, Bevernage JJL, van Nostrum CF, van Steenbergen MJ, Flesch FM, Verrijk R, de Leede L, Crommelin DJA, Hennink WE. Small oligomeric micelles based on end group modified mPEG-oligocaprolactone with monodisperse hydrophobic blocks. Macromolecules. 2007;40(1):116–22.

    Article  Google Scholar 

  27. Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release. 2002;82(2–3):189–212.

    Article  Google Scholar 

  28. Mahmud A, Xiong XB, Lavasanifar A. Novel poly(ethylene oxide)-block-poly(ε-caprolactone) block copolymers with functional side groups on the polyester block for drug delivery. Macromolecules. 2006;39(26):9419–28.

    Article  Google Scholar 

  29. Yokoyama M, Opanasopit P, Okano T, Kawano K, Maitani Y. Polymer design and incorporation methods for polymeric micelle carrier system containing water-insoluble anti-cancer agent camptothecin. J Drug Target. 2004;12(6):373–84.

    Article  Google Scholar 

  30. Lin JP, Zhang SN, Chen T, Lin SL, Jin HT. Micelle formation and drug release behavior of polypeptide graft copolymer and its mixture with polypeptide block copolymer. Int J Pharm. 2007;336(1):49–57.

    Article  Google Scholar 

  31. Kumaresh SS. DCW. Tan, Yang YY. pH-Triggered thermally responsive polymer core-shell nanoparticles for drag delivery. Adv Mater. 2005;17(3):318–23.

    Article  Google Scholar 

  32. W Xun, Wang HY, Li ZY, Cheng SX, Zhang XZ, Zhuo RX. Self-assembled micelles of novel graft amphiphilic copolymers for drug controlled release. Colloids Surf B 2011;85(1):86-91.

    Google Scholar 

  33. Tan JJ, Li YX, Liu RG, Kang HL, Wang DQ, Ma L, Liu WY, Wu M, Huang Y. Micellization and sustained drug release behavior of EC-g-PPEGMA amphiphilic copolymers. Carbohyd Polym. 2010;81(2):213–8.

    Article  Google Scholar 

Download references

Acknowledgments

We are grateful for the financial support of National Natural Science Foundation of China (No. 21074098) and National Key Basic Research Program of China (2011CB606202, 2009CB930301).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Feng He.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 99 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiang, T., Li, Y., Lv, Y. et al. Biodegradable amphiphilic block-graft copolymers based on methoxy poly(ethylene glycol)-b-(polycarbonates-g-polycarbonates) for controlled release of doxorubicin. J Mater Sci: Mater Med 25, 131–139 (2014). https://doi.org/10.1007/s10856-013-5057-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-013-5057-4

Keywords

Navigation