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Anticancer Drug-Loaded Nanospheres Based on Biodegradable Amphiphilic ε-Caprolactone and Carbonate Copolymers

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ABSTRACT

Purpose

The aim was to investigate anticancer drug-loaded poly(carbonate-ester) nanospheres as potential drug delivery systems for cancer therapy.

Methods

Functional poly(carbonate-ester) copolymers (HPCP-SD) were synthesized by the incorporation of sulfadiazine as the tumor-targeting groups to hydroxyl groups of poly(carbonate-ester) copolymers. Two types of anticancer drug-loaded poly(carbonate-ester) nanospheres I and II were further prepared by dialysis method and high-voltage electrostatic field-assisted atomization, respectively, using HPCP-SD as polymeric carriers. These carriers and anticancer drug-loaded nanospheres were characterized, and their properties in vitro and in vivo were evaluated.

Results

These anticancer drug-loaded poly(carbonate-ester) nanospheres had steady drug release rates and good controlled release properties. Moreover, anticancer drug-loaded poly(carbonate-ester) nanospheres II had faster drug release rates than those of anticancer drug-loaded nanospheres I. These anticancer drug-loaded nanospheres possessed lower cytotoxicity to HEK 293 cells and exhibited obviously higher anticancer efficiencies to the HeLa tumor cells than that of 5-fluorouracil. Anticancer drug-loaded nanospheres I possessed lower cytotoxicity to HEK 293 cells and higher anticancer activity to HeLa cells than those of anticancer drug-loaded nanospheres II.

Conclusions

These anticancer drug-loaded poly(carbonate-ester) nanospheres showed the potential as drug delivery systems for cancer therapy.

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REFERENCES

  1. Park K, Lee S, Kang E, Kim K, Choi K, Kwon IC. New generation of multifunctional nanoparticles for cancer imaging and therapy. Adv Funct Mater. 2009;19:1553–66.

    Article  CAS  Google Scholar 

  2. Tokiwa Y, Calabia BP, Ugwu CU, Aiba S. Biodegradability of Plastics. Int J Mol Sci. 2009;10:3722–42.

    Article  CAS  PubMed  Google Scholar 

  3. Norowski PA, Bumgardner JD. Biomaterial and antibiotic strategies for peri-implantitis: a review. J Biomed Mater Res B Appl Biomater. 2009;88B(2):530–43.

    Article  CAS  Google Scholar 

  4. Chawla JS, Amiji MM. Biodegradable poly(epsilon-caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen. Int J Pharm. 2002;249:127–38.

    Article  CAS  PubMed  Google Scholar 

  5. Yan GP, Zhuo RX, Zheng CY. Study on the anticancer drug 5-fluorouracil-conjugated polyaspart-amides containing hepatocyte-targeting group. J Bioact Compatible Polym. 2001;16(4):277–93.

    Article  CAS  Google Scholar 

  6. Yan GP, Zhuo RX, Zhang X, Zhang X, Li LY, Liu ML. Tumor-selective macromolecular MRI contrast agents. J Bioact Compatible Polym. 2002;17(2):139–51.

    Article  CAS  Google Scholar 

  7. Yan GP, Zhuo RX. Research progress of magnetic resonance imaging contrast agents. Chin Sci Bull. 2001;46(7):531–8.

    Google Scholar 

  8. Yan GP, Li H, Bottle SE, Cheng SX, Wang XG, Yew YK, et al. Preparation, properties and mathematical modeling of microparticle drug delivery systems based on biodegradable amphiphilic tri-block copolymers. J Appl Polym Sci. 2004;92:3869–73.

    Article  CAS  Google Scholar 

  9. Li H, Yan GP, Wu SN, Wang ZJ, Lam KY. Numerical simulation of controlled nifepine release from chitosan microspheres. J Appl Polym Sci. 2004;93:1928–37.

    Article  CAS  Google Scholar 

  10. Yan GP, Peng L, Jian SQ, Li L, Bottle SE. Spin probes for electron paramagnetic resonance imaging. Chin Sci Bull. 2008;53(24):3777–89.

    Article  CAS  Google Scholar 

  11. Yan GP, Robinsonand L, Hogg P. Magnetic resonance imaging contrast agents: overview and perspectives. Radiography. 2007;13:e5–19.

    Article  Google Scholar 

  12. Yan GP, Zhuo RX, Zhang X, Xu MY, Li LY, Ye ZH. Hepatic targeting macromolecular MRI contrast agents. Polym Int. 2002;51:892–8.

    Article  CAS  Google Scholar 

  13. Yan GP, Zhang JY, Zhou JX, Bottle SE, Yu XH, Wu JY, Li L. Targeted contrast agents for molecular imaging in magnetic resonance imaging (MRI). Recent Advances of Bioconjugate Chemistry in Molecular Imaging (ISBN 978-81-0210-7), Chen XY, Ed. 2008; Chapter 19: 371–98, Research Signpost, Kerala, India.

  14. Liao LQ, Liu LJ, Zhang C, He F, Zhuo RX. Heating characteristics and polymerization of ε-caprolactone under microwave irradiation. J Appl Polym Sci. 2003;90:2657–64.

    Article  CAS  Google Scholar 

  15. Barbault-Foucher S, Grefa R, Russo P. Design of poly-vepsiln-caprolactone nanospheres coated with bioadhesive hyaluronic acid for ocular delivery. J Control Release. 2002;83:365–75.

    Article  CAS  PubMed  Google Scholar 

  16. Sun H, Mei L, Song C, Cui X, Wang P. The in vivo degradation, absorption and excretion of PCL-based implant. Biomaterials. 2006;27:1735–40.

    Article  CAS  PubMed  Google Scholar 

  17. Brown AH, Sheares VV. Amorphous unsaturated aliphatic polyesters derived from dicarboxylic monomers synthesized by diels − Alder chemistry. Macromolecules. 2007;40:4848–53.

    Article  CAS  Google Scholar 

  18. Albertsson AC, Eklund M. Synthesis of copolymers of 1, 3-dioxan-2-one and oxepan-2-one using coordination catalysts. J Polym Sci Part A Polym Chem. 1994;32:265–79.

    Article  CAS  Google Scholar 

  19. Pego AP, Poot AA, Grijpma DW, Grijpma DW, Feijen J. Copolymers of trimethylene carbonate and epsilon-caprolactone for porous nerve guides: synthesis and properties. J Biomater Sci Polym Ed. 2001;12:35–53.

    Article  CAS  PubMed  Google Scholar 

  20. Feng YK, Zhang SF. Hydrophilic-hydrophobic AB diblock copolymers containing poly(trimethylene carbonate) and poly(ethylene oxide) blocks. J Polym Sci Part A Polym Chem. 2005;43:4819–27.

    Article  CAS  Google Scholar 

  21. Zurita R, Puiggali J, Franco L, Rodriguez-Galan A. Copolymerization of glycolide and trimethylene carbonate. J Polym Sci Part A: Polym Chem. 2006;44:993–1013.

    Article  CAS  Google Scholar 

  22. Dobrzynski P, Kasperczyk J. Synthesis of biodegradable copolymers with low-toxicity zirconium compounds. V. multiblock and random copolymers of L-lactide with trimethylene carbonate obtained in copolymerizations initiated with zirconium(IV) acetylacetonate. J Polym Sci Part A: Polym Chem. 2006;44:3184–201.

    Article  CAS  Google Scholar 

  23. Hu B, Yan GP, Zhuo RX, Wu Y, Fan CL. Polycarbonate microspheres containing tumor necrosis factor-α genes and magnetic powder as potential cancer therapeutics. J Appl Polym Sci. 2008;107(5):3343–9.

    Article  CAS  Google Scholar 

  24. Kricheldorf HR, Weegen-Schulz B. Polymers of carbonic acid 11. reactions and polymerizations of aliphatic cyclocarbonates with boron halides. Macromolecules. 1993;26:5991–5.

    Article  CAS  Google Scholar 

  25. Kricheldorf HR, Weegen-Schulz B. Polymers of carbonic acid. XIV. high molecular weight poly(trimethylene carbonate) by ring-opening polymerization with butyltin chlorides as initiators. J Polym Sci Polym Chem. 1995;33(13):2193–201.

    Article  CAS  Google Scholar 

  26. Matsuo J, Aoki K, Sanda F, Endo T. Substituent effect on the anionic equilibrium polymerization of six-membered cyclic carbonates. Macromolecules. 1998;31:4432–8.

    Article  CAS  Google Scholar 

  27. Liu ZL, Zhang JM, Zhuo RX. Synthesis and characterization of functional polycarbonates. Chem J Chin Universities. 2003;24(9):1730–2.

    CAS  Google Scholar 

  28. Mei LL, Yan GP, Yu XH, Yu XH, Cheng SX, Wu JY. Ring-opening copolymerization and properties of polycarbonate copolymers. J Appl Polym Sci. 2008;108:93–8.

    Article  CAS  Google Scholar 

  29. Chen H, Yan GP, Li L, Ai CW, Yu XH, Wu JY. Synthesis, characterization and properties of ε-caprolactone and carbonate copolymers. J Appl Polym Sci. 2009;114(5):3087–96.

    Article  CAS  Google Scholar 

  30. Lu K, Yan GP, Chen H, Li L, Ai CW, Yu XH. Microwave-assisted ring-opening copolymerization of ε-caprolactone and 2-phenyl-5, 5-bis(oxymethyl) trimethylene carbonate. Chin Sci Bull. 2009;54(18):3237–43.

    Article  CAS  Google Scholar 

  31. Huang JL, Wang HY, Zhou CL. Ring-opening polymerization of ethylene oxide by anion initiation using sulfadiazine as parent compound. J Appl Polym Sci. 1995;58:8–11.

    Google Scholar 

  32. Yan GP, Zheng CY, Cao W, Li W, Li LY, Liu ML, et al. Synthesis and preliminary evaluation of gadolinium complexes containing sulfonamide groups as potential MRI contrast agents. Radiography. 2003;9:35–41.

    Article  Google Scholar 

  33. Yan GP, Liu ML, Li LY. Studies on polyaspartamide gadolinium complexes containing sulfadiazine groups as MRI contrast agents. Bioconjug Chem. 2005;16:967–71.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGEMENTS

We thank the Hi-Tech Research and Development Program of China (Grant No. 2007AA0218-09), National Natural Science Foundation of China (Grant No.50773060), New Century Excellent Talents in University, State Education Ministry (Grant No.[2007]70: NCET-07-0649), Key National Natural Science Foundation of Hubei Province of China (Grant No. 2009CDA052), and Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (Grant No.[2007]1108) and Wuhan Scientific and Technological Project (No. 201060623274), Hubei Province, China for their financial support.

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Authors and Affiliations

  1. School of Material Science and Engineering, Wuhan Institute of Technology, Wuhan, 430074, China

    Guo-Ping Yan, Rong-Feng Zong, Liang Li, Ting Fu, Fan Liu & Xiang-Hua Yu

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  1. Guo-Ping Yan
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  2. Rong-Feng Zong
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  3. Liang Li
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  5. Fan Liu
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Correspondence to Guo-Ping Yan.

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Yan, GP., Zong, RF., Li, L. et al. Anticancer Drug-Loaded Nanospheres Based on Biodegradable Amphiphilic ε-Caprolactone and Carbonate Copolymers. Pharm Res 27, 2743–2752 (2010). https://doi.org/10.1007/s11095-010-0275-7

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  • DOI: https://doi.org/10.1007/s11095-010-0275-7

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