Macromolecular Research

The Polymer Society of Korea (한국고분자학회)
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Biotin-Conjugated Block Copolymeric Nanoparticles as Tumor-Targeted Drug Delivery Systems

  • Kim, So-Yeon (Division of Engineering Education, College of Engineering, Chungnam National University) ;
  • Cho, Seung-Hea (School of Chemical Engineering, College of Engineering, Hanyang University) ;
  • Lee, Young-Moo (School of Chemical Engineering, College of Engineering, Hanyang University)
  • Published : 2007.12.31
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Abstract

To achieve targeted drug delivery for chemotherapy, a ligand-mediated nanoparticulate drug carrier was designed, which could identity a specific receptor on the surfaces of tumor cells. Biodegradable poly(ethylene oxide)/poly$({\varepsilon}-caprolactone)$ (PEG/PCL) amphiphilic block copolymers coupled to biotin ligands were synthesized with a variety of PEG/PCL compositions. Block copolymeric nanoparticles harboring the anticancer drug paclitaxel were prepared via micelle formation in aqueous solution. The size of the biotin-conjugated PEG/PCL nanoparticles was determined by light scattering measurements to be 88-118 nm, depending on the molecular weight of the block copolymer, and remained less than 120 nm even after paclitaxel loading. From an in vitro release study, biotin-conjugated PEG/PCL nanoparticles containing paclitaxel evidenced sustained release profiles of the drug with no initial burst effect. The biotin-conjugated PEG/PCL block copolymer itself evidenced no significant adverse effects on cell viability at $0.005-1.0{\mu}g/mL$ of nanoparticle suspension regardless of cell type (normal human fibroblasts and HeLa cells). However, biotin-conjugated PEG/PCL harboring paclitaxel evidenced a much higher cytotoxicity for cancer cells than was observed in the PEG/PCL nanoparticles without the biotin group. These results showed that the biotin-conjugated nanoparticles could improve the selective delivery of paclitaxel into cancer cells via interactions with over-expressed biotin receptors on the surfaces of cancer cells.

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References

  1. C. S. S. R. Kumar, J. Hormes, and C. Leuschner, Nanofabrication Towards Biomedical Applications, Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim, Germany, 2005
  2. V. P. Torchilin, Eur. J. Pharm. Sci., 11, S81 (2000)
  3. S. Drotleff, U. Lungwitz, M. Breunig, A. Dennis, T. Blunk, J. Tessmar, and A. Gopferich, Eur. J. Pharm. Biopharm., 58, 385 (2004) https://doi.org/10.1016/j.ejpb.2004.03.018
  4. M. Shadidi and M. Sioud, Drug Resist. Update, 6, 363 (2003) https://doi.org/10.1016/j.drup.2003.11.002
  5. Z. Xu, W. Gu, J. Huang, H. Sui, Z. Zhou, Y. Yang, Z. Yan, and Y. Li, Int. J. Pharm., 288, 361 (2005) https://doi.org/10.1016/j.ijpharm.2004.10.009
  6. G. Russell-Jones, K. McTavish, J. McEwan, J. Rice, and D. Nowotnik, J. Inorg. Biochem., 98, 1625 (2004) https://doi.org/10.1016/j.jinorgbio.2004.07.009
  7. S. Majumdar, S. Duvvuri, and A. K. Mitra, Adv. Drug Deliver. Rev., 56, 1437 (2004) https://doi.org/10.1016/j.addr.2004.02.006
  8. P. Sapra and T. M. Allen, Prog. Lipid Res., 42, 439 (2003) https://doi.org/10.1016/S0163-7827(03)00032-8
  9. G. M. Dubowchik and M. A. Walker, Pharmacol. Therapeut., 83, 67 (1999)
  10. Z. M. Qian, H. Li, H. Sun, and K. Ho, Pharmacol. Rev., 54, 561 (2002)
  11. K. Na, T. B. Lee, K. Park, E. Shin, Y. Lee, and H. Choi, Eur. J. Pharm. Sci., 18, 165 (2003) https://doi.org/10.1016/S0928-0987(02)00257-9
  12. I. Brigger, C. Dubernet, and P. Couvreur, Adv. Drug Deliver. Rev., 54, 631 (2002)
  13. J. A. Hubbell, Science, 300, 595 (2003) https://doi.org/10.1126/science.1083625
  14. G. Riess, Prog. Polym. Sci., 28, 1107 (2003) https://doi.org/10.1016/S0079-6700(03)00015-7
  15. N. Nishyama, Y. Bae, K. Miyata, S. Fukushima, and K. Kataoka, Drug Discov. Today: Technologies, 2, 21 (2005) https://doi.org/10.1016/j.ddtec.2005.05.007
  16. K. Miyata, Y. Kakizawa, N. Nobuhiro, and Y. Yamasaki, J. Control. Release, 109, 15 (2005) https://doi.org/10.1016/j.jconrel.2005.09.043
  17. Y. Kakizawa, S. Furukawa, A. Ishii, and K. Kataoka, J. Control. Release, 111, 368 (2006) https://doi.org/10.1016/j.jconrel.2006.01.004
  18. Arnida, N. Nishiyama, N. Kanayama, W.-D. Jang, Y. Yamasaki, and K. Kataoka, J. Control. Release, 115, 208 (2006) https://doi.org/10.1016/j.jconrel.2006.07.014
  19. A. Harada and K. Kataoka, Prog. Polym. Sci., 31, 949 (2006) https://doi.org/10.1016/j.progpolymsci.2006.09.004
  20. C. P. Leamon and J. A. Reddy, Adv. Drug Deliver. Rev., 56, 1127 (2004) https://doi.org/10.1016/j.addr.2004.01.008
  21. Y. Lu and P. S. Low, J. Control. Release, 91, 17 (2003) https://doi.org/10.1016/S0168-3659(03)00215-3
  22. Y. Lu, E. Sega, and C. P. Low, Adv. Drug Deliver. Rev., 56, 1161 (2004) https://doi.org/10.1016/j.addr.2004.01.009
  23. H. S. Yoo and T. G. Park, J. Control. Release, 96, 273 (2004) https://doi.org/10.1016/j.jconrel.2004.02.003
  24. E. K. Park, S. B. Lee, and Y. M. Lee, Biomaterials, 26, 1053 (2005) https://doi.org/10.1016/j.biomaterials.2004.04.008
  25. I. G. Shin, S. Y. Kim, Y. M. Lee, C. S. Cho, and Y. K. Sung, J. Control. Release, 51, 1 (1998)
  26. S. Y. Kim, I. G. Shin, Y. M. Lee, C. S. Cho, and Y. K. Sung, J. Control. Release, 51, 13 (1998)
  27. S. Y. Kim and Y. M. Lee, Biomaterials, 22, 1697 (2001) https://doi.org/10.1016/S0142-9612(00)00074-0
  28. S. Y. Kim, Y. M. Lee, H. J. Shin, and J. S. Kang, Biomaterials, 22, 2049 (2001) https://doi.org/10.1016/S0142-9612(00)00074-0
  29. S. Y. Kim, Y. M. Lee, D. J. Baik, and J. S. Kang, Biomaterials, 24, 55 (2003) https://doi.org/10.1016/S0142-9612(02)00248-X
  30. S. Y. Kim, I. G. Shin, and Y. M. Lee, J. Control. Release, 56, 197 (1998)
  31. S. Y. Kim, I. G. Shin, and Y. M. Lee, Biomaterials, 20, 1033 (1999)
  32. J. C. Ha, S. Y. Kim, and Y. M. Lee, J. Control. Release, 62, 381 (1999)
  33. S. Y. Kim, J. C. Ha, and Y. M. Lee, J. Control. Release, 65, 348 (2000)
  34. V. R. Sinha, K. Bansal, R. Kaushik, R. Kumria, and A. Trehan, Int. J. Pharm., 278, 1 (2004) https://doi.org/10.1016/j.ijpharm.2004.01.044
  35. A. Babizon, A. T. Horowitz, D. Goren, D. Tzemach, F. M. Shavit, M. M. Qazen, and S. Zalipsky, Bioconjugate Chem., 10, 289 (1999)
  36. D. Dube, M. Francis, J. C. Leroux, and F. M. Winnik, Bioconjugate Chem., 13, 685 (2002)
  37. J. Lee, S. C. Lee, G. Acharya, C. Chang, and K. Park, Pharmaceut. Res., 20, 1022 (2003) https://doi.org/10.1023/A:1024458206032
  38. E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, and M. S. Lee, Rapid Commun. Mass Sp., 12, 620 (1998)