화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Polymer(Korea), Vol.24, No.5, 728-735, September, 2000
Export Citation
지속적인 국소 마취를 위한 생분해성 PLGA 미립구의 제조와 생체외 방출 거동
Preparation of Biodegradable PLGA Microspheres for Sustained Local Anesthesia and Their in vitro Release Behavior
조진철, 강길선, 최학수, 이종문, 이해방1, †
  • 전북대학교 고분자공학과
  • 1한국화학연구소 생체고분자팀
Jin Cheol Cho, Gilson Khang, Hak-Soo Choi, John M. Rhee, and Hai Bang Lee1, †
  • Department of Polymer Science and Technology, Chonbuk National University, 664-14, Dukjin Dong 1Ga, Dukjin Ku, Chonju 561-756, Korea
  • 1Biomaterials Laboratory, Korea Research Institute of Chemical Technology, P. O. Box 107, Yusugn, Taejon 305-343, Korea
E-mail:
초록
지속적인 국소 마취의 가능성을 연구하기 위하여 펜타닐이 함유된 생분해서 poly(L-lactic-co-glycolide) (75 : 25 락타이드와 글리콜라이드의 몰 비, PLGA0미립구를 제조하였다. 펜타닐 베이스가 함유된 PLGA 미립구는 일반적인 O/W 용매 증발법으로 제조하였으며 미립구의 크기는 10에서 150㎛의 범위에 있었다. 미립구의 표면과 단면 형태를 전자현미경으로 관찰하였고 생체의 펜타닐 베이스 방출량은 HPLC로 분석하였다. 젤라틴 유화제의 사용으로 가장 낮은 다공성 단면의 형태와 가장 높은 포접율을 가질 수 있었다. 펜타닐의 방출 패턴은 유화제의 종류, PLGA의 분자량 및 농도, 초기 약물 loading 양 등과 같은 제조 조건들의 영향이 미치는 것으로 관찰되었다. 생체외에서 펜타닐 베이스의 방출은 제조 조건을 조절함으로써 거의 zero-order 형태로 25일 이상을 지속적이었다. 또한 XRD와 DSC로 펜타닐이 함유된 PLGA 미립구의 물리화학적인 성질을 조사하였다.
Fentanyl-loaded biodegradable poly(L-lactide-co-glycolide) (75:25 by mole ratio of lactide to glycolide, PLGA) microspheres (MSs) were prepared to study the possibility for long-acting local anesthesia. We developed the fentanyl base(FB, slightly water-soluble)-loaded PLGA MSs by means of conventional O/W solvent evaporation method. The size of MSs was in the range of 10∼150㎛. The morphology of MSs was characterized by SEM, and the in vitro release amounts of FB were analyzed by HPLC. The lowest porous cross-sectional morphology and the highest encapsulation efficiency were obtained by using gelatin as an emulsifiber. The influences of several preparation parameters, such as emulsifer types, molecular weights and concentrations of PLGA, and initial drug loading amount, etc., have been observed in the release patterns of FB. The release of FB in in vitro was more prolonged over 25 days, with close to zero-order pattern by controlling the preparation parameters. We also investigated the physicochemical properties of FB-loaded PLGA MSs by X-ray diffraction and differential scanning calorimeter.
Keywords:fentanyl base;PLGA microspheres;solvent evaporation method;encapsulation efficiency;phsicochemical properties
  1. Poklis A, Clinical Toxicology, 33(5), 439 (1995)
  2. Southan MA, Anti-Cancer Drugs, 6(3), 29 (1995) 
  3. Miguel R, Kreitzer JM, Reinhart D, Sebel PS, Bowie J, Freedman G, Eisenkraft JB, Anesthesiology, 83(3), 470 (1995) 
  4. Dewell WM, Khandaghabadi M, D'Souza MJ, Solomon HM, Am. J. Hosp. Pharm., 12, 243 (1994)
  5. Gesztes A, Mezei M, Anesth. Analg., 67, 1079 (1988)
  6. Langerman L, Golomb E, Benita S, Anesthesiology, 74, 105 (1991)
  7. Kwon H, Khang G, Song HY, Lee HB, Polym.(Korea), 23(3), 421 (1999)
  8. Lee HB, Khang G, Cho JC, Rhee JM, Lee JS, "Controlled Drug Deliverty," eds. by K. Park, and R.J. Mrsny, ACS Symposium Series No. 752, p. 385, ACS, Washington, DC, 2000 (2000)
  9. Khang G, Jeon JH, Lee JW, Cho SC, Lee HB, Bio-Med. Mater. Eng., 7(6), 357 (1997)
  10. Holland SJ, Tighe BJ, Gould PL, J. Control. Release, 4, 155 (1986) 
  11. Khang G, Jeon JH, Cho JC, Rhee JM, Lee HB, Polym.(Korea), 23(6), 861 (1999)
  12. Williams DF, Mort E, J. Bioeng., 1, 231 (1997)
  13. Bostaman O, J. Bone Joint Surg., 73A(1), 148 (1991)
  14. Singhal JP, Singh H, Ray AR, Rev. Macromol. Chem. Phys., C28, 475 (1988)
  15. Hollinger OJ, Schmitz JP, J. Oral Maxillofac. Surg., 45, 594 (1987)
  16. Cho JC, Khang G, Rhee JM, Kim YS, Lee JS, Lee HB, Korea Polym. J., 7(2), 79 (1999)
  17. Khang G, Cho JC, Lee JW, Rhee JM, Lee HB, Bio-Med. Mater. Eng., 9(1), 49 (1999)
  18. Khang G, Lee JH, Lee JW, Cho JC, Lee HB, Korea Polym. J., 8(2), 80 (2000)
  19. Wakiyama N, Juni K, Nakano M, Chem. Pharm. Bull., 30(7), 2621 (1982)
  20. Kosima T, Nakano M, Juni K, Inoue S, Yoshida Y, Chem. Pharm. Bull., 32(7), 2795 (1984)
  21. Wakiyama N, Juni K, Nakano M, Chem. Phram. Bull., 30(10), 3719 (1982)
  22. Kolli M, Montheard JP, Vergnaud JM, Int. J. Pharm., 81, 103 (1992) 
  23. Bonbomme L, Benhamou D, Bengre T, Int. J. Pharm., 84, 33 (1992) 
  24. Jalil R, Nixon JR, J. Microencapsul., 7(3), 297 (1990)
  25. Iwata M, MeGinity JW, Pharm. Res., 10(8), 1219 (1993) 
  26. Seilinger K, Lanzo C, Sekut A, J. Pharm. Biomed. Anal., 12, 243 (1994) 
  27. Bansal R, Aranda JV, J. Liq. Chrom. Rel. Technol., 19(3), 353 (1996)
  28. Jeffery H, Davis SS, O'Hagan DT, Int. J. Pharm., 77, 169 (1991) 
  29. Fitzgerald JF, Corrigan OI, J. Control. Release, 42, 125 (1996)