화학공학소재연구정보센터
Polymer(Korea), Vol.32, No.2, 143-149, March, 2008
Pioglitazone 가용화를 위한 PEG-PLA(PLGA) 고분자 미셀의 제조 및 특성분석
Preparation and Characterization of PEG-PLA(PLGA) Micelles for Solubilization of Pioglitazone
E-mail:
초록
생체적합성을 가진 친수성 poly(ethylene glycol)(PEG)블록과 생분해성 고분자인 poly(D,L-lactide) (PLA) 또는 poly(lactide-co-glycolide)(PLGA)를 소수성 블록으로 하는 양친성 이중 블록공중합체를 합성하여 난용성 당뇨병 치료제인 pioglitazone의 가용화를 위한 고분자 미셀을 제조하였다. PEG 말단으로부터 LA의 개환중합에 의해 합성된 고분자의 화학적 조성과 분자량은 반응액 내 당량비로 조절하였고, 합성된 고분자는 수용액 상에서 10∼30 nm 크기인 구형의 자기조립 미셀을 형성하였다(CMC=0.001∼0.0076 mg/mL). 투석법과 고체분산법을 이용하여 약물을 봉입한 후 AFM, DLS, HPLC 분석을 통하여 미셀의 특성을 비교하였다. 결론적으로 PEG-PLA (또는 PLGA) 공중합체를 이용한 고체분산법을 통해 pioglitazone을 효과적으로 가용화시킬 수 있었다.
We synthesized PEG-PLA(or PLGA) amphiphilic di-block copolymers, which consist of PEG as biocompatible and hydrophilic block and PLA(or PLGA) as biodegradable and hydrophobic block, by ring opening polymerization of LA in the presence of methoxy PEG as a macroinitiator. The compositions and the molecular weights of the copolymers were controlled by changing the feed ratio of LA(and GA) to PEG initiator. The di-block copolymers could self-assemble in aqueous media to form micellar structure. A hydrophobic model drug, pioglitazone, was loaded into the polymer micelle using solid dispersion and dialysis methods, and the drug-loaded micelles were characterized by AFM, DLS and HPLC measurements. The drug loading capacity and in vitro release studies were performed and evaluated under various conditions. These results indicated that the amphiphilic di-block copolymers of PEGPLA (or PLGA) could solubilize pioglitazone by solid dispersion method and the drug release was modulated according to micellar chemical compositions.
  1. Blanco E, Bey EA, Dong Y, Weinberg BD, SuttonDM, Boothman DA, Gao J, J. Control. Release, 122, 365 (2007)
  2. Blanco E, Bey EA, Dong Y, Weinberg BD, Sutton DM, Boothman DA, Gao J, J. Control. Release, 72, 191 (2001)
  3. Huh KM, Lee SC, Cho YW, Lee J, Jeong JH, Park K, J. Control. Release, 101, 59 (2005)
  4. Lavasanifar A, Samuel J, Kwon GS, Adv. Drug Deliv. Rev., 54, 169 (2002)
  5. Liggins RT, Burt HM, Adv. Drug Deliv. Rev., 54, 191 (2002)
  6. Xu JP, Ji J, Chen WD, Shen JC, J. Control. Release, 107, 502 (2005)
  7. Yamamoto Y, Yasugi K, Harada A, Nagasaki Y, Kataoka K, J. Control. Release, 82, 359 (2002)
  8. Cho YW, Lee J, Lee SC, Huh KM, Park K, J. Control. Release, 97, 249 (2004)
  9. Na K, Lee KH, Lee DH, Bae YH, Eur. J. Pharm. Sci., 27, 115 (2006)
  10. Zhang J, Jiang W, Zhao X, Wang Y, Tsinghua Science & Technology, 12, 493 (2007)
  11. Ooya T, Huh KM, Saitoh M, Tamiya E, Park K, Science and Technology of Advanced Materials, 6, 452 (2005)
  12. Kwon GS, Kataoka K, Adv. Drug Deliv. Rev., 16, 295 (1995)
  13. Kwon GS, Okano T, Adv. Drug Deliv. Rev., 21, 107 (1996)
  14. Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC, J. Control. Release, 109, 169 (2005)
  15. Park TG, Lu W, Crotts G, J. Control. Release, 33, 211 (1995)
  16. Liu HB, Jiang A, Guo JA, Uhrich KE, J. Polym. Sci. A: Polym. Chem., 37(6), 703 (1999)
  17. Bae YH, Huh KM, Kim Y, Park KH, J. Control. Release, 64, 3 (2000)
  18. Huh KM, Bae YH, Polymer, 40(22), 6147 (1999)
  19. Lavasanifar A, Samuel J, Kwon GS, J. Control. Release, 77, 155 (2001)
  20. Agrawal SK, Sanabria-DeLong N, Coburn JM, Tew GN, Bhatia SR, J. Control. Release, 112, 64 (2006)
  21. Rai AK, Rai DK, Spectroc. Acta, 59, 1673 (2003)
  22. Radhakrishna T, Sreenivas Rao D, Om Reddy G, J. Pharmaceut. Biomed. Anal., 29, 593 (2002)
  23. Sripalakit P, Neamhom P, Saraphanchotiwitthaya A, J. Chromatogr. B, 843, 164 (2006)
  24. Xue YJ, Turner KC, Meeker JB, Pursley J, Arnold M, Unger S, J. Chromatogr. B, 795, 215 (2003)
  25. Burt HM, Zhang X, Toleikis P, Embree L, Hunter WL, Colloids Surf. B: Biointerfaces, 16, 161 (1999)
  26. Adams ML, Andes DR, Kwon GS, Biomacromolecules, 4, 750 (2003)
  27. Adams ML, Kwon GS, J. Control. Release, 87, 23 (2003)