Folate가 수식된 Poly((R)-3-hydroxy butyrate)-Poly(ethylene glycol) 나노입자를 이용한 표적지향형 약물전달체

권승호; 김영진; Seung Ho Kwon; Young Jin Kim

Polymer(Korea), Vol.33, No.6, 515-519, November, 2009

Targeted Drug Delivery Carriers Using Folate Conjugated Poly((R)-3-hydroxy butyrate)-Poly(ethylene glycol) Nanoparticles

권승호, 김영진 ^†

충남대학교 공과대학 바이오응용화학과

Seung Ho Kwon, and Young Jin Kim^†

Department of Applied Chemistry & Biological Engineering, Chungnam National University, 79, Daehangno, Yuseong-gu, Daejeon 305-764, Korea

E-mail:

초록

생분해성 고분자인 poly((R)-3-hydroxy butyrate)와 poly(ethylene glycol)을 결합시켜 양친성 이중 블록 공중합체를 형성하였고, 표적인자인 folate를 수식하여 특정 암세포에 표적화하도록 설계하였다. 이 공중합체는 수용액상에서 미셀을 이루며, DLS로 측정한 결과, 125∼156 nm의 크기였고, 동결건조하여 SEM으로 관찰한 결과 구형임을 확인하였다. 여기에 소수성 약물인 griseofulvin을 사용하여, 35∼56%의 봉입률을 나타내었다. 약물은 in vitro 상에서 24시간 동안 지속적으로 방출되었다. 세포생존율을 측정하여, folate가 수식된 입자가 그렇지 않은 입자보다 약 10% 더 낮은 세포생존율을 보임으로써 표적지향 효과가 있다는 것을 알 수 있었다.

Biodegradable poly((R)-3-hydroxy butyrate) and poly(ethylene glycol) was conjugated to make amphiphilic di-block copolymer. Folate was conjugated at di-block copolymer to target the cancer cells. Copolymer was ready to form the self-assembled micelle whose size was 125∼156 nm in aqueous solution. Griseofulvin as a hydrophobic drug was loaded in nanoparticles. Their loading efficiencies were 35∼56%. Hydrophobic drug was continuously released for 24 h. Cell viability test showed that folate attached particles were 10% more efficient than the particles without targeting ligands.

Keywords:PHB;PEG;folate;targeting;drug delivery

[References]

Kim HS, Hong SB, Sung HJ, Moon GA, Yoon Y, Korean Journal of Pharmacognosy, 34, 145 (2003)
Kim NJ, Sim SB, Kim JK, Won DH, Hong ND, Korean Journal of Pharma, 29, 93 (1998)
Antony AC, The Journal of The American Society of Hematology, 79, 2807 (1992)
Mathias CJ, Wang S, Low PS, Waters DJ, Green MA, Nucl. Med. Biol., 26, 23 (1999)
Gaucher G, Dufresne M, Sant VP, Kand N, Maysinger D, Leroux J, J. Control. Release, 109, 169 (2005)
Jeong KH, Kim YJ, Polym.(Korea), 30(6), 512 (2006)
Anderson AJ, Dawes EA, Microbiol. Rev., 54, 450 (1990)
Schiavon O, Pasut G, Moro S, Orsolini P, Guiotto A, Veronese FM, Eur. J. Med. Chem., 39, 123 (2004)
Zalipsky S, Qazen M, Walker Ⅱ JA, Mullah N, Quinn YP, Huang SK, Bioconjugate Chem., 10, 703 (1999)
Jedlinski Z, Kurcok P, Lenz RW, Macromolecules, 31(19), 6718 (1998)
Zhao Q, Cheng GX, Li HM, Ma XL, Zhang LG, Polymer, 46(23), 10561 (2005)
Li J, Li X, Ni XP, Leong KW, Macromolecules, 36(8), 2661 (2003)
Yoo HS, Park TG, J. Control. Release, 96, 273 (2004)
Chambers E, Diane M, Wagrowski D, Ziling L, Jeffery R, Mazzeo, J. Chromatrogr. B, 852, 1 (2007)
Li J, Li X, Ni X, Wang X, Li H, Leong KW, Biomaterials, 27, 4132 (2006)
Hyun H, Kim MS, Khang G, Rhee JM, Lee HB, Polym.(Korea), 30(2), 146 (2006)
Lukyanov AN, Gao Z, Torchilin VP, J. Control. Release, 91, 97 (2003)
Liu H, Farrell S, Uhrich K, J. Control. Release, 68, 167 (2000)
Ram BP, Tyle P, Pharmaceut. Res., 4, 181 (1987)
Lee ES, Na K, Bae YH, J. Control. Release, 91, 103 (2003)
Bae YH, Huh KM, Kim Y, Park KH, J. Control. Release, 64, 3 (2000)
Lu Y, Low PS, Cancer Immunol. Immun., 51, 153 (2002)
Park EK, Kim SY, Lee SB, Lee YM, J. Control. Release, 109, 158 (2005)
Allen C, Maysinger D, Eisenberg A, Colloid Surfa B, 16, 3 (1999)
Aliabadi HM, Elhasi S, Majmud A, Gulamjusein R, Mahdipoor P, Lavasanifar A, Int. J. Pharm., 329, 158 (2007)

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[1] Kim HS, Hong SB, Sung HJ, Moon GA, Yoon Y, Korean Journal of Pharmacognosy, 34, 145 (2003)

[2] Kim NJ, Sim SB, Kim JK, Won DH, Hong ND, Korean Journal of Pharma, 29, 93 (1998)

[3] Antony AC, The Journal of The American Society of Hematology, 79, 2807 (1992)

[4] Mathias CJ, Wang S, Low PS, Waters DJ, Green MA, Nucl. Med. Biol., 26, 23 (1999)

[5] Gaucher G, Dufresne M, Sant VP, Kand N, Maysinger D, Leroux J, J. Control. Release, 109, 169 (2005)

[6] Jeong KH, Kim YJ, Polym.(Korea), 30(6), 512 (2006)

[7] Anderson AJ, Dawes EA, Microbiol. Rev., 54, 450 (1990)

[8] Schiavon O, Pasut G, Moro S, Orsolini P, Guiotto A, Veronese FM, Eur. J. Med. Chem., 39, 123 (2004)

[9] Zalipsky S, Qazen M, Walker Ⅱ JA, Mullah N, Quinn YP, Huang SK, Bioconjugate Chem., 10, 703 (1999)

[10] Jedlinski Z, Kurcok P, Lenz RW, Macromolecules, 31(19), 6718 (1998)

[11] Zhao Q, Cheng GX, Li HM, Ma XL, Zhang LG, Polymer, 46(23), 10561 (2005)

[12] Li J, Li X, Ni XP, Leong KW, Macromolecules, 36(8), 2661 (2003)

[13] Yoo HS, Park TG, J. Control. Release, 96, 273 (2004)

[14] Chambers E, Diane M, Wagrowski D, Ziling L, Jeffery R, Mazzeo, J. Chromatrogr. B, 852, 1 (2007)

[15] Li J, Li X, Ni X, Wang X, Li H, Leong KW, Biomaterials, 27, 4132 (2006)

[16] Hyun H, Kim MS, Khang G, Rhee JM, Lee HB, Polym.(Korea), 30(2), 146 (2006)

[17] Lukyanov AN, Gao Z, Torchilin VP, J. Control. Release, 91, 97 (2003)

[18] Liu H, Farrell S, Uhrich K, J. Control. Release, 68, 167 (2000)

[19] Ram BP, Tyle P, Pharmaceut. Res., 4, 181 (1987)

[20] Lee ES, Na K, Bae YH, J. Control. Release, 91, 103 (2003)

[21] Bae YH, Huh KM, Kim Y, Park KH, J. Control. Release, 64, 3 (2000)

[22] Lu Y, Low PS, Cancer Immunol. Immun., 51, 153 (2002)

[23] Park EK, Kim SY, Lee SB, Lee YM, J. Control. Release, 109, 158 (2005)

[24] Allen C, Maysinger D, Eisenberg A, Colloid Surfa B, 16, 3 (1999)

[25] Aliabadi HM, Elhasi S, Majmud A, Gulamjusein R, Mahdipoor P, Lavasanifar A, Int. J. Pharm., 329, 158 (2007)