화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Macromolecular Research, Vol.15, No.7, 623-632, December, 2007
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Preparation and Characterization of Nanoparticles Using Poly(N-isopropylacrylamide)-Poly(ε-caprolactone) and Poly(ethylene glycol)-Poly(ε-caprolactone) Block Copolymers with Thermosensitive Function
Changyong Choi, Mi-Kyeong Jang, and Jae-Woon Nah†
  • Department of Polymer Science and Engineering, Sunchon National University, Suncheon 540-742, Korea
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Thermosensitive nanoparticles were prepared via the self-assembly of two different poly(ε-caprolactone)-based block copolymers of poly(N-isopropylacrylamide)-b-poly(ε-caprolactone) (PNPCL) and poly(ethylene glycol)-b-poly(ε-caprolactone) (PEGCL). The self-aggregation and thermosensitive behaviors of the mixed nanoparticles were investigated using 1H-NMR, turbidimetry, differential scanning microcalorimetry (micro-DSC), dynamic light scattering (DLS), and fluorescence spectroscopy. The copolymer mixtures (mixed nanoparticles, M1-M5, with different PNPCL content) formed nano-sized self-aggregates in an aqueous environment via the intra- and/or intermolecular association of hydrophobic PCL chains. The microscopic investigation of the mixed nanoparticles showed that the critical aggregation concentration (cac), the partition equilibrium constants (Kv) of pyrene, and the aggregation number of PCL chains per one hydrophobic microdomain varied in accordance with the compositions of the mixed nanoparticles. Furthermore, the PNPCL harboring mixed nanoparticles evidenced phase transition behavior, originated by coil to the globule transition of PNiPAAm block upon heating, thereby resulting in the turbidity change, endothermic heat exchange, and particle size reduction upon heating. The drug release tests showed that the formation of the thermosensitive hydrogel layer enhanced the sustained drug release patterns by functioning as an additional diffusion barrier.
Keywords:nanoparticles;thermosensitive;PCL;PNiPAAm;PEG;drug delivery
  1. Hubbell JA, Science, 300, 595 (2003)
  2. Kwon S, Park JH, Chung H, Kwon IC, Jeong SY, Kim IS, Langmuir, 19(24), 10188 (2003)
  3. Kataoka K, Harada A, Nagasaki Y, Adv. Drug Deliv. Rev., 47, 113 (2001)
  4. Lee KY, Jo WH, Kwon IC, Kim YH, Jeong SY, Macromolecules, 31(2), 378 (1998)
  5. Hrkach JS, Peracchia MT, Domb A, Lotan N, Langer R, Biomaterials, 18, 27 (1997)
  6. Riley T, Stolnik S, Heald CR, Xiong CD, Garnett MC, Illum L, Davis SS, Purkiss SC, Barlow RJ, Gellert PR, Langmuir, 17(11), 3168 (2001)
  7. Ruan G, Feng SS, Biomaterials, 24, 5037 (2003)
  8. Brus C, Petersen H, Aigner A, Caubayko F, Kissel T, Bioconjugate Chem., 15, 677 (2004)
  9. Yamamoto Y, Nagasaki Y, Kato Y, Sugiyama Y, Kataoka K, J. Control. Release, 77, 27 (2001)
  10. Xu JP, Ji J, Chen WD, Shen JC, J. Control. Release, 107, 502 (2005)
  11. Venkatraman SS, Jie P, Min F, Freddy BY, Leong-Huat G, Int. J. Pharm., 298, 219 (2005)
  12. Opanasopit P, Yokoyama M, Watanabe M, Kawano K, Maitani Y, Okano T, Pharm. Res., 21, 2001 (2004)
  13. Zeng FQ, Liu JB, Allen C, Biomacromolecules, 5(5), 1810 (2004)
  14. Cho H, Chung D, Jeongho A, Biomaterials, 25, 3733 (2004)
  15. Zhou S, Deng X, Yang H, Biomaterials, 24, 3563 (2003)
  16. Francis MF, Piredda M, Winnik FM, J. Control. Release, 93, 55 (2003)
  17. Yoo HS, Lee JE, Chung H, Kwon IC, Jeong SY, J. Control. Release, 103, 235 (2005)
  18. Jung SW, Jeong YI, Kim SH, Int. J. Pharm., 254, 109 (2003)
  19. Akiyoshi K, Kobayashi S, Shichibe S, Mix D, Baudys M, Kim SW, Sunamoto J, J. Control. Release, 54, 313 (1998)
  20. Lee KY, Jo WH, Kwon IC, Kim YH, Jeong SY, Macromolecules, 31(2), 378 (1998)
  21. Kataoka K, Kwon GS, Yokoyama M, Okano T, Sakurai Y, J. Control. Release, 24, 119 (1993)
  22. Matsumura Y, Maeda H, Cancer Res., 46, 6387 (1986)
  23. Kwon G, Naito M, Yokoyama M, Okano T, Sakurai Y, Kataoka K, J. Control. Release, 48, 195 (1997)
  24. Zhang XZ, Wang FJ, Chu CC, J. Mater. Sci. -Mater. Med., 14, 451 (2003)
  25. Zhang X, Wu D, Chu CC, Biomaterials, 25, 4719 (2004)
  26. Verestiu L, Ivanov C, Barbu E, Tsibouklis J, Int. J. Pharm., 269, 185 (2004)
  27. Kim S, Healy KE, Biomacromolecules, 4(5), 1214 (2003)
  28. Makino K, Hiyoshi J, Ohshima H, Colloids Surf. B: Biointerfaces, 20, 341 (2001)
  29. Jeong B, Bae YH, Lee DS, Kim SW, Nature, 388(6645), 860 (1997)
  30. Jeong B, Kim SW, Bae YH, Adv. Drug Deliv. Rev., 54, 37 (2002)
  31. Vernon B, Kim SW, Bae YH, J. Biomed. Mater. Res., 51, 69 (2000)
  32. Neradovic D, Soga O, Van Nostrum CF, Hennink WE, Biomaterials, 25, 2409 (2004)
  33. Kohori F, Sakai K, Aoyagi T, Yokoyama M, Sakurai Y, Okano T, J. Control. Release, 55, 87 (1998)
  34. Uchida K, Sakai K, Ito E, Kwon OH, Kikuchi A, Yamato M, Okano T, Biomaterials, 21, 923 (2000)
  35. Chung JE, Yokoyama M, Aoyagi T, Sakurai Y, Okano T, J. Control. Release, 53, 119 (1998)
  36. Chung JE, Yokoyama M, Yamato M, Aoyagi T, Sakurai Y, Okano T, J. Control. Release, 62, 115 (1999)
  37. Kohori F, Sakai K, Aoyagi T, Yokoyama M, Yamato M, Sakurai Y, Okano T, Colloids Surf. B: Biointerfaces, 16, 19 (1999)
  38. Kohori F, Yokoyama M, Sakai K, Okano T, J. Control. Release, 78, 155 (2002)
  39. Lee SC, Chang YK, Yoon JS, Kim CH, Kwon IC, Kim YH, Jeong SY, Macromolecules, 32(6), 1847 (1999)
  40. Yuan ML, Wang YH, Li XH, Xiong CD, Deng XM, Macromolecules, 33(5), 1613 (2000)
  41. Zhang G, Niu A, Peng S, Jiang M, Tu Y, Li M, Wu C, Accounts Chem. Res., 34, 249 (2001)
  42. Albertsson AC, Varma IK, Biomacromolecules, 4(6), 1466 (2003)
  43. Lele BS, Leroux JC, Macromolecules, 35(17), 6714 (2002)
  44. Soo PL, Luo LB, Maysinger D, Eisenberg A, Langmuir, 18(25), 9996 (2002)
  45. Harada A, Kataoka K, Macromolecules, 28(15), 5294 (1995)
  46. Harada A, Kataoka K, Macromolecules, 31(2), 288 (1998)
  47. Akiyoshi K, Deguchi S, Tajima H, Nishikawa T, Sunamoto J, Macromolecules, 30(4), 857 (1997)
  48. Lee KY, Jo WH, Kwon IC, Kim YH, Jeong SY, Langmuir, 14(9), 2329 (1998)
  49. Kwon S, Park JH, Chung H, Kwon IC, Jeong SY, Kim IS, Langmuir, 19(24), 10188 (2003)
  50. Turro NJ, Yekta A, J. Am. Chem. Soc., 100, 5951 (1978)
  51. Heald CR, Stolnik S, Kujawinski KS, De Matteis C, Garnett MC, Illum L, Davis SS, Purkiss SC, Barlow RJ, Gellert PR, Langmuir, 18(9), 3669 (2002)
  52. Alami E, Almgren M, Brown W, Francois J, Macromolecules, 29(6), 2229 (1996)
  53. Han SK, Na K, Bae YH, Colloids Surf. A: Physicochem. Eng. Asp., 214, 49 (2003)
  54. Wilhelm M, Zhao CL, Wang Y, Xu R, Winnik MA, Mura JL, Riess GM, Croucher D, Macromolecules, 24, 1033 (1991)
  55. Lee SC, Chang YK, Yoon JS, Kim CH, Kwon IC, Kim YH, Jeong SY, Macromolecules, 32(6), 1847 (1999)
  56. Lele BS, Leroux JC, Macromolecules, 35(17), 6714 (2002)