화학공학소재연구정보센터
Polymer(Korea), Vol.26, No.4, 535-542, July, 2002
계면활성제를 사용하지 않는 Poly(DL-lactide-co-glycolide) 나노입자로부터의 Norfloxacin 방출과 생분해 특성
Norfloxacin Release from Surfactant-Free Nanoparticles of Poly(DL-lactide-co-glycolide) and Biodegradation
E-mail:
초록
투석법을 이용하여 계면활성제를 사용하지 않는 poly(DL-lactide-co-glycolide)(PLGA) 나노입자를 제조하고 다양한 용매에 따른 입자 크기, 약물 함유량, 생분해도 등과 같은 물리ㆍ화학적 특성을 조사하였다. Dimethylacetamide (DMAc), dimethylformamide (DMF), dimethylsulfoxide (DMSO)로 제조된 PLGA 나노입자의 크기는 acetone으로 제조한 입자보다 적었다. 또한, 약물 함유량은 DMAc>DMF>DMSO=acetone 순서였다. PLGA 나노입자는 scanning electron microscopy (SEM)과 transmission electron microscopy (TEM)의 측정으로 구형임을 알 수 있었다. 계면활성제를 사용하지 않는 나노입자에 봉입된 norfloxacin (NFx)은 X-ray diffraction 분석을 통하여 입자 표면에 약물을 가지지 않는 좋은 약물 봉입 효율을 가짐을 알 수 있었다. 모델약물로 사용된 NFx의 방출속도는 약물 함유량뿐만 아니라 입자크기에 의해 좌우된다. 또한 PLGA 나노입자의 분해속도는 아세톤보다는 DMF를 사용하였을 때 더 빠르며 이는 PLGA 나노입자의 생분해성도 입자크기에 좌우된다는 것을 알 수 있었다.
We have prepared the surfactant-free nanoparticles of poly(DL-lactide-co-glycolide)(PLGA) by dialysis method and their physicochemical properties such as particle size and drug contents were investigated against various solvent. The size of PLGA nanoparticles prepared by using dimethylacetamide (DMAc), dimethylformamide (DMF), and dimethylsulfoxide (DMSO) was smaller than that from acetone. Also, the order of drug contents was DMAc>DMF>DMSO = acetone. These phenomena could be expected from the fact that solvent affects the size of nanoparticles and drug contents. The PLGA nanoparticles have a good spherical shapes as observed from scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Also, surfactant-free nanoparticles entrapping norfloxacin (NFx) have a good drug loading capacity without free-drug on the surface of nanoparticles confirmed by the analysis of X-ray powder diffraction. Release kinetics of NFx used as a model drug was governed not only by drug contents but also by particle size. Also, the biodegradation rate of PLGA nanoparticles prepared from DMF was faster than that prepared from acetone, indicating that the biodegradation of PLGA nanoparticles is size-dependent.
  1. Couvreur P, Fattal E, Andremont A, Pharm. Res., 8, 1079 (1991) 
  2. Couvreur P, Fattal E, Alphandary H, Puisieux F, Andremont A, J. Control. Release, 19, 259 (1992) 
  3. Leroux JC, Allemann E, Jaeghere FD, Doelker E, Gurny R, J. Control. Release, 39, 339 (1996) 
  4. Allemann E, Gurny R, Doelker E, J. Pharm., 39(5), 173 (1993)
  5. Davis SS, Pharmaceut. Technol., 5, 71 (1981)
  6. Seijo B, Fattal E, Roblot-Treupel L, Couvreur P, J. Pharm., 62, 1 (1990)
  7. Holland SJ, Tighe BJ, Gould PL, J. Control. Release, 4, 155 (1986) 
  8. Khang G, Jeon JH, Lee JW, Cho SC, Lee HB, Bio-Med. Mater. Eng., 7, 357 (1997)
  9. Ciftci K, SuheylaKas H, Hincal AA, Ercan TM, Guven O, Ruacan S, J. Pharm., 131, 73 (1996)
  10. Jeffery H, Davis SS, Ohagan DT, J. Pharm., 77, 169 (1991)
  11. Scholes PD, Coombes AGA, Illum L, Davis SS, Vert M, Davies MC, J. Control. Release, 25, 145 (1993) 
  12. Sjostrom B, Kronberg B, Carlfors J, J. Pharm. Sci., 82, 579 (1993) 
  13. Witschi C, Doelker E, Eur. J. Pharm. Biopharm., 43, 215 (1997) 
  14. Jeong YI, Cheon JB, Kim SH, Nah JW, Lee YM, Sung YK, Akaike T, Cho CS, J. Control. Release, 51, 169 (1998) 
  15. Kwon GS, Naito M, Yokoyama M, Okano T, Sakurai Y, Kataoka K, Pharm. Res., 12, 192 (1995) 
  16. Lasic DD, Nature, 355, 279 (1992) 
  17. Nah JW, Jeong YI, Cho CS, J. Polym. Sci. B: Polym. Phys., 36(3), 415 (1998) 
  18. Ogawa Y, Okada H, Yamamoto M, Shimamito T, Chem. Pharm. Bull., 36, 2576 (1988)
  19. Lisa BP, J. Pharm., 116, 1 (1995)
  20. La SB, Okano T, Kataoka K, J. Pharm. Sci., 85, 85 (1996) 
  21. Kim SY, Shin IG, Lee YM, Biomaterials, 20, 1033 (1999) 
  22. Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R, Science, 263(5153), 1600 (1994) 
  23. Govender T, Stolnik S, Garnett MC, Illum L, Davis SS, J. Control. Release, 57, 171 (1999) 
  24. Peracchia MT, Gref R, Minamitake Y, Domb A, Lotan N, Langer R, J. Control. Release, 46, 223 (1997) 
  25. Alleman E, Gurny R, Doelker E, Eur. J. Pharm. Biopharm., 39, 173 (1993)