Article
  • Characteristics of BCNU-loaded PLGA Wafers
  • An TK, Kang HJ, Lee JS, Seong H, Jeong JK, Khang G, Hong Y, Lee HB
  • BCNU를 함유한 생분해성 PLGA 웨이퍼의 특성분석
  • 안태군, 강희정, 이진수, 성하수, 정제교, 강길선, 홍용길, 이해방
Abstract
Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea(BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor for the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape(diamenter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of the wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.

항암제가 함유된 생분해성 고분자 디바이스를 이용한 국소전달요법은 종양 부위에 고농도로 약물을 전달시킬 수 있는 이유로 약물의 효율성을 증가시킬 수 있다. 1,3-bis(2-chloroethyl)-1-nitro-sourea(BCNU, carmustine)는 뇌종양 치료를 위하여 가장 일반적으로 사용되는 화학요법적 약물이다. 표적 부위까지 항암제를 효과적으로 전달하기 위한 이식제의 설계는 중요한 인자이다. 본 연구에서 약물의 방출경향을 조절하기 위해서 생분해성 웨이퍼의 첨가제와 다양한 제형 변화로부터 BCNU의 방출패턴을 조사하였다. 각각 3.85, 10, 20 및 30%의 BCNU를 함유한 PLGA 웨이퍼를 다양한 형태(직경 3, 5 및 10 mm, 두께 0.5, 1 및 2 mm)로 직접 압축성형법에 의해 제조하였다. 생체외 방출실험에서 BCNU 함유 PLGA 웨이퍼로부터 약물 방출거동은 웨이퍼의 초기 약물 함유량, 무게, 직경, 두께, 부피, 표면적 및 PLGA 분자량뿐만 아니라 첨가제의 종류와 같은 다양한 변수로 조절했다. 웨이퍼로부터 약물의 방출은 BCNU 함유량 및 염화나트륨(NaCl)과 폴리엔비닐피롤리돈(PVP)이 증가할수록 촉진되었다. 또한, BCNU가 함유된 PLGA 웨이퍼의 무게와 형태변화에 대한 조사를 통하여 다양한 기하학적 인자들과 첨가제의 효과를 고찰하였다.

Keywords: brain tumor; BCNU; PVP; NaCl; wafers

References
  • 1. Moon DS, Khang G, Seong HS, Rhee JM, Lee JS, Lee HB, Biomater. Res., 4, 107 (2000)
  •  
  • 2. Black PM, N. Eng. J. Med., 324, 1471 (1991)
  •  
  • 3. Harbaugh RE, Sanders RL, Reeder RF, Neurosurgery, 23, 693 (1988)
  •  
  • 4. Penn RD, York MM, Paice JA, J. Neurosurg., 83, 215 (1995)
  •  
  • 5. Kreuter J, Alyautdin RN, Kharkevich DA, Ivanov AA, Brain Res., 674, 171 (1995)
  •  
  • 6. Bickel U, Yoshikawa T, Pardridge WM, Adv. Drug. Deliv. Rev., 10, 205 (1993)
  •  
  • 7. Lindvall O, Bjorklund A, Acta Neurol. Scand., 126, 197 (1989)
  •  
  • 8. Gage FH, Wolff JA, Rosenberg MB, Xu L, Yee JK, Shults C, Friedmann T, Neuroscience, 23, 795 (1987)
  •  
  • 9. Khang G, Lee HBBiomedical Polymer, Korean Chemical Society Press, Munundang, Seoul, Korea (2001)
  •  
  • 10. Cho JC, Khang G, Rhee JM, Kim YS, Lee JS, Lee HB, Korea Polym. J., 7(2), 79 (1999)
  •  
  • 11. Khang G, Cho JC, Lee JW, Rhee JM, Lee HB, Bio-Med. Mater. Eng., 9, 49 (1999)
  •  
  • 12. Lee HB, Khang G, Cho JC, Rhee JM, Lee JS, Polym. Prepr., 40, 288 (1999)
  •  
  • 13. Khang G, Lee JH, Lee JW, Cho JC, Lee HB, Korea Polym. J., 8(2), 80 (2000)
  •  
  • 14. Cho JC, Khang G, Choi HS, Rhee JM, Lee HB, Polym.(Korea), 24(5), 728 (2000)
  •  
  • 15. Son WI, Yun DI, Khang G, Kim BS, Lee HB, Biomater. Res., 4, 92 (2000)
  •  
  • 16. Cho JC, Khang G, Rhee JM, Kim YS, Lee JS, Lee HB, Biomater. Res., 4, 136 (2000)
  •  
  • 17. Seo SA, Choi HS, Lee DH, Khang G, Lee HB, Polym.(Korea), 25(6), 884 (2001)
  •  
  • 18. Seo SA, Choi HS, Cho JC, Khang G, Rhee JM, Lee HB, Biomater. Res., 5, 35 (2001)
  •  
  • 19. Choi HS, Khang G, Shin HC, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002)
  •  
  • 20. Seo SA, Choi HS, Cho JC, Khang G, Rhee JM, Lee HB, Int. J. Pharm., 239, 93 (2002)
  •  
  • 21. Lee HB, Khang G, Cho JC, Rhee JM, Lee JSFentanyl-Loaded PLGA Microspheres for local anesthesia, in Controlled Drug Delivery; Desigging Technologies for the Future, eds. by K. Park and R.J. Mrnsy, p. 385, ACS Symp. Series 752, Washington D.C. (2000)
  •  
  • 22. Tamargo RJ, Myseros JS, Epstein JI, Jang MB, Chasin M, Brem H, Cancer Res., 53, 329 (1993)
  •  
  • 23. Walter KA, Cahan MA, Gur A, Tyler B, Hilton J, Colvin OM, Burger PC, Domb A, Brem H, Cancer Res., 54, 2207 (1994)
  •  
  • 24. Lillehei KO, Kong Q, Withrow SJ, Kleinschmidts B, Neurosurgery, 39, 1191 (1996)
  •  
  • 25. Minie P, boisdron-Cller M, Croue A, Guy G, Benoit JP, Neurosurgery, 39, 117 (1996)
  •  
  • 26. Brem H, Mahaley MS, Vick NA, Black KL, Schold SC, Ellier TW, Cozzens JW, Kenealy JN, J. Neurosurg., 74, 441 (1991)
  •  
  • 27. Brem H, Ewend MG, Piantadosi S, Greehoot J, Burger PC, Sisti M, J. NeuroOncol., 26, 111 (1995)
  •  
  • 28. Khang G, Rhee JM, Lee JS, Lee HB, Polym. Sci. Technol., 12(1), 4 (2001)
  •  
  • 29. Seong HS, Moon DS, Khang G, Lee HB, Macromol. Chem. Symp., 14, 95 (2001)
  •  
  • 30. Seong H, Moon DS, Khang G, Lee JS, Lee HB, Polym.(Korea), 26(1), 128 (2002)
  •  
  • 31. An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)
  •  
  • 32. Iwata M, Ueda H, Drug. Dev. Ind. Pharm., 22, 1161 (1996)
  •  
  • 33. Lu WG, Zhang Y, Xiong QM, Bao YC, Chen QH, Chin. Pharm. J., 30, 24 (1995)
  •  
  • 34. Chowdary KP, Ramesh KV, Ind. Drugs., 32, 477 (1995)
  •  
  • 35. Loo TL, Dion RL, Dixon RL, Rall DP, J. Pharm. Sci., 55, 492 (1966)
  •  
  • 36. Fredrikson K, Lundgren P, Acta Pharm. Scand., 23, 115 (1986)
  •  
  • 37. Leigh S, Carless JE, Burt BW, J. Pharm. Sci., 56, 888 (1967)
  •  
  • 38. Moussa IS, Cartilier LH, Int. J. Pharm., 149, 139 (1997)
  •  
  • 39. Shivan P, Sprockel OL, Int. J. Pharm., 158, 83 (1997)
  •  
  • 40. Trikkonen S, Paronen P, Int. J. Pharm., 88, 39 (1992)
  •  
  • 41. Trikkonen S, Paronen P, Int. J. Pharm., 92, 55 (1993)
  •  
  • 42. McDonald C, Richardson C, J. Pharmacol., 33, 38 (1981)
  •  
  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2023 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 2002; 26(5): 691-700

    Published online Sep 25, 2002

  • Received on Jul 5, 2002
  • Accepted on Sep 10, 2002