Polymer(Korea) (폴리머)

The Polymer Society of Korea (한국고분자학회)
권호 표지

Preparation and Characterization of PEG-PLA(PLGA) Micelles for Solubilization of Rosiglitazone

Rosiglitazone 가용화를 위한 PEG-PLA(PLGA) 고분자 미셀의 제조 및 특성분석

  • Kim, Yon-Hwan (Department of Polymer Science and Engineering, Chungnam National University) ;
  • Im, Jeong-Hyuk (Department of Polymer Science and Engineering, Chungnam National University) ;
  • Min, Hyun-Su (Department of Polymer Science and Engineering, Chungnam National University) ;
  • Kim, Jun-Ki (Department of Chemical and Biological Engineering, Chungju National University) ;
  • Lee, Yong-Kyu (Department of Chemical and Biological Engineering, Chungju National University) ;
  • Park, Go-Eun (Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Uijeongbu St. Mary's Hospital) ;
  • Cho, Kwang-Jae (Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Uijeongbu St. Mary's Hospital) ;
  • Huh, Kang-Moo (Department of Polymer Science and Engineering, Chungnam National University)
  • 김연환 (충남대학교 고분자공학) ;
  • 임정혁 (충남대학교 고분자공학) ;
  • 민현수 (충남대학교 고분자공학) ;
  • 김준기 (충주대학교 화공생물공학) ;
  • 이용규 (충주대학교 화공생물공학) ;
  • 박고은 (가톨릭대학교 의과대학 이비인후과학교실) ;
  • 조광재 (가톨릭대학교 의과대학 이비인후과학교실) ;
  • 허강무 (충남대학교 고분자공학)
  • Received : 2010.01.12
  • Accepted : 2010.02.08
  • Published : 2010.05.25
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, PEG-PLA(or PLGA) amphiphilic di-block copolymers were synthesized by ring opening polymerization of D,L-lactide(or glycolide) and applied to polymeric micelle system for solubilization of a rosiglitazone as diabetes drug. The drug could be efficiently loaded into the polymer micelle by solid dispersion technique, and the drug-loaded micelles were characterized and evaluated as a drug delivery carrier by fluorescence spectrometer, DSC, and DLS measurements. The colloidal stability of drug loaded micelles in aqueous media could be enhanced by addition of 2-hydroxy-N-picolylnitinamide as a hydrotropic agent. The polymer micelles also showed biocompatible and nontoxic properties in vitro cell viability using MTT assay, and the drug loaded micelles were observed to be more effective than free drug for decreasing glucose in blood of rats.

본 실험에서는 일련의 poly(ethylene glycol)-poly(D,L-lactide)(또는 -poly(D,L-lactide-co-glycolide))이중블록 공중합체들을 D,L-lactide(또는 glycolide)의 고리열림 중합에 의해 합성하고, 당뇨병 치료제 일종인 rosiglitazone의 가용화를 위한 고분자 미셀 제형으로서의 특성을 평가하였다. 고체분산법을 이용하여 높은 봉입률의 약물함유 미셀 제형을 효과적으로 제조하였고, 미셀 제형의 수용액 내 안정성을 hydrotropic agent의 일종인 2-hydroxy-N-picolylnitinamide(HPNA)의 사용으로 더욱 향상시킬 수 있었다. 생체 외 세포생존평가에서 생체적합성과 낮은 독성을 보였고, 쥐를 이용한 동물실험에서도 약물을 함유한 고분자 미셀이 약물 대조군보다 혈당을 보다 효과적으로 감소시켰다.

Keywords

References

  1. S. K. Agrawal, N. Sanabria-DeLong, J. M. Coburn, G. N. Tew, and S. R. Bhatia, J. Control. Release, 112, 64 (2006). https://doi.org/10.1016/j.jconrel.2005.12.024
  2. E. Blanco, E. A. Bey, Y. Dong, B. D. Weinberg, D. M. Sutton, D. A. Boothman, and J. Gao, J. Control. Release, 122, 365 (2007). https://doi.org/10.1016/j.jconrel.2007.04.014
  3. J.-P. Xu, J. Ji, W.-D. Chen, and J.-C. Shen, J. Control. Release, 107, 502 (2005). https://doi.org/10.1016/j.jconrel.2005.06.013
  4. A. Lavasanifar, J. Samuel, and G. S. Kwon, J. Control. Release, 77, 155 (2001). https://doi.org/10.1016/S0168-3659(01)00477-1
  5. T. G. Park, W. Lu, and G. Crotts, J. Control. Release, 33, 211 (1995). https://doi.org/10.1016/0168-3659(94)00084-8
  6. R. T. Liggins and H. M. Burt, Adv. Drug Deliv. Rev., 54, 191 (2002). https://doi.org/10.1016/S0169-409X(02)00016-9
  7. L. Hongbo, J. Anna, G. Jian, and E. U. Kathryn, J. Polym. Sci. Part A: Polym. Chem., 37, 703 (1999). https://doi.org/10.1002/(SICI)1099-0518(19990315)37:6<703::AID-POLA5>3.0.CO;2-O
  8. Y. H. Bae, K. M. Huh, Y. Kim, and K.-H. Park, J. Control. Release, 64, 3 (2000). https://doi.org/10.1016/S0168-3659(99)00126-1
  9. K. M. Huh and Y. H. Bae, Polymer, 40, 6147 (1999). https://doi.org/10.1016/S0032-3861(98)00822-2
  10. G. Gaucher, M.-H. Dufresne, V. P. Sant, N. Kang, D. Maysinger, and J.-C. Leroux, J. Control. Release, 109, 169 (2005). https://doi.org/10.1016/j.jconrel.2005.09.034
  11. G. S. Kwon and T. Okano, Adv. Drug Deliv. Rev., 21, 107 (1996) https://doi.org/10.1016/S0169-409X(96)00401-2
  12. S. C. Kim, D. W. Kim, Y. H. Shim, J. S. Bang, H. S. Oh, S. W. Kim, and M. H. Seo, J. Control. Release, 72, 191 (2001). https://doi.org/10.1016/S0168-3659(01)00275-9
  13. K. M. Huh, S. C. Lee, Y. W. Cho, J. Lee, J. H. Jeong, and K. Park, J. Control. Release, 101, 59 (2005). https://doi.org/10.1016/j.jconrel.2004.07.003
  14. A. Lavasanifar, J. Samuel, and G. S. Kwon, Adv. Drug Deliv. Rev., 54, 169 (2002). https://doi.org/10.1016/S0169-409X(02)00015-7
  15. Y. Yamamoto, K. Yasugi, A. Harada, Y. Nagasaki, and K. Kataoka, J. Control. Release, 82, 359 (2002). https://doi.org/10.1016/S0168-3659(02)00147-5
  16. Y. W. Cho, J. Lee, S. C. Lee, K. M. Huh, and K. Park, J. Control. Release, 97, 249 (2004). https://doi.org/10.1016/j.jconrel.2004.03.013
  17. K. Na, K. H. Lee, D. H. Lee, and Y. H. Bae, Eur. J. Pharm. Sci., 27, 115 (2006). https://doi.org/10.1016/j.ejps.2005.08.012
  18. T. Ooya, K. M. Huh, M. Saitoh, E. Tamiya, and K. Park, Sci. Tech. Adv. Mater., 6, 452 (2005). https://doi.org/10.1016/j.stam.2005.01.006
  19. J. H. Im, Y.-K. Lee, and K. M. Huh, Polymer(Korea), 32, 143 (2008).
  20. B. L. Kolte, B. B. Raut, A. A. Deo, M. A. Bagool, and D. B. Shinde, J. Chromatogr. B, 788, 37 (2003). https://doi.org/10.1016/S1570-0232(02)01011-5
  21. J. M. Malinowski and S. Bolesta, Clin. Ther., 22, 1151 (2000). https://doi.org/10.1016/S0149-2918(00)83060-X
  22. G. Derosa, S. A. T. Salvadeo, A. D'Angelo, E. Fogari, P. D. Ragonesi, L. Ciccarelli, M. N. Piccinni, I. Ferrari, A. Gravina, P. Maffioli, and A. F. Cicero, Arch. Med. Res., 39, 412 (2008). https://doi.org/10.1016/j.arcmed.2007.12.009
  23. M. Hanefeld, R. Patwardhan, and N. P. Jones, Nutr. Metab. Cardiovasc. Diseases, 17, 13 (2007). https://doi.org/10.1016/j.numecd.2005.12.003
  24. K. M. Huh, H. S. Min, S. C. Lee, H. J. Lee, S. Kim, and K. Park, J. Control. Release, 126, 122 (2008). https://doi.org/10.1016/j.jconrel.2007.11.008
  25. C. R. E. Mansur, L. S. Spinelli, E. F. Lucas, and G. Gonzalez, Colloids Surf. A: Physicochem. Eng. Aspects, 149, 291 (1999). https://doi.org/10.1016/S0927-7757(98)00417-8
  26. S. C. Lee, G. Acharya, J. Lee, and K. Park, Macromolecules, 36, 2248 (2003). https://doi.org/10.1021/ma021629k
  27. K. G. Tolman and J. Chandramouli, Clin. Liver. Dis., 7, 369 (2003) https://doi.org/10.1016/S1089-3261(03)00020-5
  28. E. L. Kennedy, R. Tchao, and P. J. Harvison, Toxicology, 186, 79 (2003). https://doi.org/10.1016/S0300-483X(02)00692-3
  29. R. Marfella, M. Portoghese, F. Ferraraccio, M. Siniscalchi, M. Babieri, C. Di Filippo, M. D'Amico, F. Rossi, and G. Paolisso, Heart, 95, 1020 (2009). https://doi.org/10.1136/hrt.2009.165969