Article
  • Effect of Molecular Weight of PLGA on Release Behavior of Doxorubicin for Double-Layered PLGA Microspheres
  • Park JS, Yang JC, Yuk SH, Shin HS, Rhee JM, Kim MS, Lee HB, Khang G
  • PLGA 분자량에 따른 이중층 독소루비신 미립구의 방출거동
  • 박정수, 양재찬, 육순홍, 신형식, 이종문, 김문석, 이해방, 강길선
Abstract
We developed the doxorubicin-loaded PLGA double-layered microspheres using relatively simple oil-in-water (O/W) solvent evaporation method for sustained release of doxorubicin and investigated the release behavior according to PLGA molecular weight and initial drug loading. The double-layered microsphere was characterized on the surface, the cross-section morphology, the behavior of doxorubicin release for 5 weeks by SEM and fluorescence spectrophotometer. Double-layered microspheres showed smooth surfaces and clear difference between core and outer-shell. As the PLGA molecular weight increased, the release rate of doxorubicin-loaded, double-layered microspheres decreased. These results showed that the release behaviors can be controlled by the variation of molecular weight of PLGA.

항암제인 독소루비신의 지속적인 방출을 위하여 PLGA와 독소루비신의 미립구를 수중유형(O/W) 용매증발 방법을 이용하여 약물의 농도와 고분자의 분자량의 변화에 따른 방출거동의 차이를 확인하였다. 이중층 미립구내의 독소루비신의 방출을 분석하기 위하여 형광 분광 광도계를 이용하여 5주 동안 독소루비신의 방출을 보았으며 주사전자현미경을 이용하여 이중층미립구의 단면과 표면을 확인하였다. 제조된 이중층 미립구는 외부층이 전체적으로 매끄러운 표면과 구형을 나타내고 있었고 이중층 미립구의 단면을 잘라 계면층을 중심으로 하여 내부형태와 외부형태를 구분 지을 수 있었다. 또한 제조된 이중층 PLGA 독소루비신 미립구는 방출 결과를 통하여 저분자량의 고분자를 이용할수록 방출이 빠르다는 것을 확인할 수 있었다. 따라서 미립구를 제조하는데 있어서 고분자의 분자량을 조절함으로써 방출거동을 조절할 수 있다는 것을 확인하였다.

Keywords: dextran; double-layered microsphere; doxorubicin; PLGA

References
  • 1. Allen TM, Cheng WW, Hare JI, Laginha KM, Anticancer Angents Med Chem., 6, 513 (2006)
  •  
  • 2. Muvaffak A, Gurhan I, Gunduz U, Hasirci N, J. Drug Target., 13, 151 (2005)
  •  
  • 3. Soppimath KS, Aminabbhavi TM, Kulharni AR, Rudzinski WE, J. Control. Release, 70, 1 (2001)
  •  
  • 4. Khang G, Kim MS, Cho SH, Lee I, Rhee JM, Lee HB, Tissue Eng. Regen. Med., 1, 9 (2004)
  •  
  • 5. Jang WY, Kim SH, Lee IW, Kim MS, Rhee JM, Khang G, Lee HB, Tissue Eng. Regen. Med., 2, 100 (2005)
  •  
  • 6. Son WI, Yun DI, Khang G, Kim BS, Lee HB, Biomater. Res., 4, 92 (2000)
  •  
  • 7. Choi HS, Kim SW, Yun DI, Khang G, Rhee JM, Kim YS, Lee HB, Polym.(Korea), 25(3), 334 (2001)
  •  
  • 8. Khang G, Cho JC, Lee JW, Rhee JM, Lee HB, Bio-Med. Mater. Eng., 9, 49 (1999)
  •  
  • 9. Seo KS, Hong KD, Hyun H, Kim MS, Khang G, Lee HB, Tissue Eng. Regen. Med., 2, 109 (2005)
  •  
  • 10. Kim SK, Hong KD, Kim SH, Kim MS, Khang G, Lee IW, Han CW, Lee HK, Lee HB, Tissue Eng. Regen. Med., 2, 130 (2005)
  •  
  • 11. Choi HS, Khang G, Shin H, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002)
  •  
  • 12. Lee SJ, Khang G, Lee YM, Lee HB, Biomater J, Sci., Polym. Ed., 13, 197 (2002)
  •  
  • 13. Seong H, Moon DS, Khang G, Lee JS, Lee HB, Polym.(Korea), 26(1), 128 (2002)
  •  
  • 14. Moon DS, Khang G, Seong HS, Rhee JM, Lee JS, Lee HB, Biomater. Res., 4, 107 (2000)
  •  
  • 15. An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)
  •  
  • 16. Cho KJ, Song DK, Oh SH, Koh YJ, Lee SH, Lee MC, Lee JH, Tissue Eng. Regen. Med., 2, 115 (2005)
  •  
  • 17. An TK, Lee JS, Shin PK, Cho SH, Kahng G, Lee HB, Macromol. Symp., 15, 339 (2002)
  •  
  • 18. An TK, Kang HJ, Lee JS, Seong H, Jeong JK, Khang G, Hong Y, Lee HB, Polym.(Korea), 26(5), 691 (2002)
  •  
  • 19. United States Pharmacopoeia XXI, Rockville, MD, USA, 357 (194)
  •  
  • 20. Arcamone F, Cassineli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C, Biotechnol. Bioeng., 11, 1101 (1969)
  •  
  • 21. Trevisan MG, Poppi RJ, Anal. Chim. Acta, 69, 493 (2003)
  •  
  • 22. United States Pharmacopoeia XXI, Rockville, MD, USA, 357 (1994)
  •  
  • 23. Missirlis D, Kawamura R, Tirelli N, Hubbell JA, Eur. J. Pharm. Sci., 29, 120 (2006)
  •  
  • 24. Cedron LA, Sayalero ML, Lanao JM, J. Chromatogr. B, 721, 271 (1999)
  •  
  • 25. Steinherz LJ, Steinherz PG, Tan CTC, Heller G, Murphy L, J. Am. Med. Assoc., 266, 1672 (1991)
  •  
  • 26. Olson RD, Mushlin PS, Faseb J., 4, 3076 (1990)
  •  
  • 27. Stridhar R, Dwivedi C, Anderson J, Baker PB, Sharma HM, Desai P, Engineer FN, J. Natl. Cancer Inst., 84, 1653 (1992)
  •  
  • 28. Arshady R, J. Bioact. Compatible Polym., 5, 315 (1990)
  •  
  • 29. Hong KD, Ahn YS, Go JT, Kim MS, Yuk SH, Shin HS, Rhee JM, Khang G, Lee HB, Polym.(Korea), 29(3), 260 (2005)
  •  
  • 30. Ko JT, Jung HJ, Mo JH, Cho JS, Yuk SH, Shin HS, Kim NS, Rhee JM, Lee HB, Khang G, Key Engineering Materials, 342, 513 (2007)
  •  
  • 31. Cheung RY, Ying Y, Rauth AM, Marcon N, Wu XY, Biomaterials, 26, 5375 (2005)
  •  
  • 32. Ko JT, Lee JH, Lee CR, Shin HS, Yuk SH, Kim MS, Khang G, Rhee JM, Lee HB, Polym.(Korea), 29(6), 543 (2005)
  •  
  • 33. Iwata M, Meginity JW, Pharmacol. Res., 10, 1219 (1990)
  •  
  • 34. Cho JC, Khang G, Choi HS, Rhee JM, Lee HB, Polym.(Korea), 24(5), 728 (2000)
  •  
  • 35. Li YP, Pei YY, Zhang XY, Gu ZH, Zhou ZH, Yuan WF, Zhou JJ, Zhu JH, Gao XJ, J. Control. Release, 71, 203 (2001)
  •  
  • 36. Miyazaki Y, Onuki Y, Yakou S, Takayama K, Int. J. Pharm., 324, 144 (2006)
  •  
  • 37. Defail AJ, Edington HD, Matthews S, Lee WC, Marra KG, J. Biomed. Mater. Res. A, 15, 954 (2006)
  •  
  • 38. Lee JS, Shin JH, Jeong JK, Rhee JM, Lee HB, Khang G, Polym.(Korea), 27(1), 9 (2003)
  •  
  • 39. Kumar MNVR, Bakowsky U, Lehr CM, Biomaterials, 25, 1771 (2004)
  •  
  • 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

  • 2007; 31(3): 189-193

    Published online May 25, 2007

  • Received on Jan 19, 2007
  • Accepted on Apr 6, 2007