폴리(에틸렌 글리콜)이 결합된 Polysuccinimide의 합성과 특성

임낙현; 이하영; 김문석; 강길선; 이해방; 조선행; Nak Hyun Lim; Ha Young Lee; Moon Suk Kim; Gilson Khang; Hai Bang Lee; Sun Hang Cho

Polymer(Korea), Vol.29, No.1, 36-40, January, 2005

Export Citation

폴리(에틸렌 글리콜)이 결합된 Polysuccinimide의 합성과 특성

Synthesis and Characterization of Poly(ethylene glycol) Grafted Polysuccinimide

임낙현, 이하영¹, 김문석 ¹, 강길선 , 이해방 ¹, 조선행 ^{1, †}

전북대학교 고분자·나노공학과
¹한국화학연구원 나노생체재료연구팀

Nak Hyun Lim, Ha Young Lee¹, Moon Suk Kim¹, Gilson Khang , Hai Bang Lee¹, and Sun Hang Cho^{1, †}

Department of Polymer·Nano Science and Technology, Chonbuk National University, 664-14, Dukjin-dong, Dukjin gu, Jeonju 561-756, Korea
¹Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology, P. O. Box 107, Yuseong, Daejon 305-506, Korea

E-mail:

초록

폴리(아미노산)유도체는 약물전달시스템의 약물전달체로 많이 연구되고 있으며 그 중 Polysuccinimide(PSI)는 생체적합성과 생분해성 등의 물리화학적 특성을 이용하여 약물전달체로 이용할 수 있는 가능성을 지닌 고분자이다. 축합중합을 이용하여 아스파르트산이 고리를 형성함으로써 PSI를 중합하였다. 이 때 PSI의 중합 최적조건을 관찰하기 위하여 시간과 촉매함량의 변화에 따른 평균분자량의 변화를 확인하였다. 또한 친수성과 소수성으로 이루어진 고분자 미셀을 제조하기 위하여 친수성 사슬인 메톡시폴리(에틸렌 글리콜((MPEG)을 결합시켰다. 합성한 고분자는 ¹H-NMR, FT-IR 및 GPC를 통하여 특성을 확인하였으며, ELS와 AFM을 통해 미셀의 형성에 대한 특성을 분석하였다. 미셀의 평균크기는 90~130 nm로 측정되었다. 본 연구를 통하여 PSI를 주사슬로 하는 가지 공중합체가 미셀 형태의 약물전달용 전달체로서 가능성을 가지고 있음을 확인할 수 있었다.

Poly(amino acid) derivatives have been widely investigated as a drug carrier in drug delivery system. Particularly,polysuccinimide (PSI) is one of the most promising drug carriers since it possesses suitable physicochemical characteristics for development of macromolecular prodrugs, due to biocompatibility and biodegradability. In this study, we deal with the synthesis of polyaspartamide having various functional groups such as methoxy-poly(ethylene glycol) (MPEG) via ring closing of PSI. PSI was synthesized by polyonensation polymerization of spartic acid. The variety of average molecular weight was confirmed with reacion time and catalyst content to observe the optimum condition of synthesis. MPEG, hydrophilic chain, was bonded to fabricate polymeric micell composed of hydrophilic and hydrophobic polymer. All materials were characterized by ¹H-NMR, FT-IR and GPC. In addition, the formation of nanoparticle micelle as drug carrier were also examined. Micelle size was measured by ELS and AFM. The functionalized polysparamide formed nanoparticle micelle whose size ranged from 90 to 130 nm. In conclusion, we prepared polyaspartamide functionalized with PEG examined the possibility as drug carriers.

Keywords:aspartic acid;polysuccinimide;biodegradable;micelle;nanoparticle graft copolymer

[References]

Muranishi S, Crit. Rev. Ther. Drug Carr. Syst., 7, 1 (2000)
Lasic D, Nature, 355, 279 (1992)
Torchilin VP, J. Control. Release, 79, 137 (2001)
Bader H, Ringsdorf H, Schmidt B, Angew. Makromol. Chem., 123-124, 457 (1984)
Kwon GS, Kataoka K, Adv. Drug Deliv. Rev., 16, 295 (1995)
Kwon GS, Okano T, Adv. Drug Deliv. Rev., 21, 107 (1996)
Kataoka K, Harada A, Nagasaki Y, Adv. Drug Deliv. Rev., 47, 113 (2001)
Caliceti P, Quarta SM, Veronese FM, Cavallaro G, Pedone E, Giammona G, Biochim. Biophy. Acta., 1528, 177 (2001)
Tomida M, Nakato T, Kuramochi M, Shibata M, Matsunami S, Kakuchi T, Polymer, 37(19), 4435 (1996)
Tomida M, Nakato T, Matsunami S, Kakuchi T, Polymer, 38, 4733 (1997)
Ouchi T, Shiratani M, Jinno M, Hirao M, Ohya Y, Macromol. Chem., 14, 825 (1993)
Hayashi T, Iwatsuki M, Biopolymers, 29, 549 (1990)
Jain GL, Ray AR, Macromol. Chem., 182, 2557 (1981)
Giammona G, Carlishi B, Palazzo S, J. Polym. Sci. A: Polym. Chem., 25, 2813 (1987)
Giammona G, Carlisi B, Pitarresi G, Fontana G, J. Bioact. Compat. Polym., 6, 129 (1991)
Giammona G, Carlisi B, Pitarresi G, Cavallaro G, Liveri VT, J. Control. Release, 22, 197 (1992)
Giammona G, Puglisi G, Cavallaro G, Spadaro A, Pitarresi G, J. Control. Release, 33, 261 (1995)
Giammona G, Cavallaro G, Fontana G, DeGuidi G, Giuffrida S, Eur. J. Pharm. Sci., 4, 273 (1996)
Pitarresi G, Palumbo FS, Giammona G, Casadei MA, Moracci FM, Biomaterials, 24, 4301 (2003)
Castelli F, Pitarresi G, Tomarchio V, Gimmona G, J. Control. Release, 45, 103 (1997)
Wout Z, Pec EA, Maggiore JA, Williams RH, Palicharla P, Johnston TP, J. Parenteral Sci. Technol., 46, 192 (1992)
Palmer WK, Emeson EE, Johnston TP, Atherosclerosis, 136, 115 (1998)
Khang G, Rhee JM, Lee JS, Lee HB, Macromol. Res., 12, 4 (2001)
Seong H, Moon DS, Khang G, Lee JS, Lee HB, Polym.(Korea), 26(1), 128 (2002)
An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)
Choi HS, Khang G, Shin H, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002)
Yokoyama M, Satoh A, Sakurai Y, Okano T, Matsumura Y, Kakizoe T, Kataoka K, J. Control. Release, 55, 219 (1998)
Batrakova EV, Dorodnych TY, Klinskii EY, Kliushnenkova EN, Shemchukova OB, Goncharova ON, Arjakov SA, Alakhov VY, Kabanov AV, Br. J. Cancer, 74, 1545 (1996)
Kataoka K, Pure Appl. Chem., A31, 1759 (1994)
Neri P, Antoni G, Benvenuti F, Cocoda F, Gazze G, J. Med. Chem., 16, 893 (1973)
Wolk SK, Swift G, Paik YH, Yocom KM, Smith RL, Simon ES, Macromolecules, 27(26), 7613 (1994)
Hong SI, Kim BC, Polym.(Korea), 6(5), 336 (1982)
Zhang Y, Zhuo R, Biomaterials, 26, 2089 (2005)

[Related Articles]

[1] Muranishi S, Crit. Rev. Ther. Drug Carr. Syst., 7, 1 (2000)

[2] Lasic D, Nature, 355, 279 (1992)

[3] Torchilin VP, J. Control. Release, 79, 137 (2001)

[4] Bader H, Ringsdorf H, Schmidt B, Angew. Makromol. Chem., 123-124, 457 (1984)

[5] Kwon GS, Kataoka K, Adv. Drug Deliv. Rev., 16, 295 (1995)

[6] Kwon GS, Okano T, Adv. Drug Deliv. Rev., 21, 107 (1996)

[7] Kataoka K, Harada A, Nagasaki Y, Adv. Drug Deliv. Rev., 47, 113 (2001)

[8] Caliceti P, Quarta SM, Veronese FM, Cavallaro G, Pedone E, Giammona G, Biochim. Biophy. Acta., 1528, 177 (2001)

[9] Tomida M, Nakato T, Kuramochi M, Shibata M, Matsunami S, Kakuchi T, Polymer, 37(19), 4435 (1996)

[10] Tomida M, Nakato T, Matsunami S, Kakuchi T, Polymer, 38, 4733 (1997)

[11] Ouchi T, Shiratani M, Jinno M, Hirao M, Ohya Y, Macromol. Chem., 14, 825 (1993)

[12] Hayashi T, Iwatsuki M, Biopolymers, 29, 549 (1990)

[13] Jain GL, Ray AR, Macromol. Chem., 182, 2557 (1981)

[14] Giammona G, Carlishi B, Palazzo S, J. Polym. Sci. A: Polym. Chem., 25, 2813 (1987)

[15] Giammona G, Carlisi B, Pitarresi G, Fontana G, J. Bioact. Compat. Polym., 6, 129 (1991)

[16] Giammona G, Carlisi B, Pitarresi G, Cavallaro G, Liveri VT, J. Control. Release, 22, 197 (1992)

[17] Giammona G, Puglisi G, Cavallaro G, Spadaro A, Pitarresi G, J. Control. Release, 33, 261 (1995)

[18] Giammona G, Cavallaro G, Fontana G, DeGuidi G, Giuffrida S, Eur. J. Pharm. Sci., 4, 273 (1996)

[19] Pitarresi G, Palumbo FS, Giammona G, Casadei MA, Moracci FM, Biomaterials, 24, 4301 (2003)

[20] Castelli F, Pitarresi G, Tomarchio V, Gimmona G, J. Control. Release, 45, 103 (1997)

[21] Wout Z, Pec EA, Maggiore JA, Williams RH, Palicharla P, Johnston TP, J. Parenteral Sci. Technol., 46, 192 (1992)

[22] Palmer WK, Emeson EE, Johnston TP, Atherosclerosis, 136, 115 (1998)

[23] Khang G, Rhee JM, Lee JS, Lee HB, Macromol. Res., 12, 4 (2001)

[24] Seong H, Moon DS, Khang G, Lee JS, Lee HB, Polym.(Korea), 26(1), 128 (2002)

[25] An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)

[26] Choi HS, Khang G, Shin H, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002)

[27] Yokoyama M, Satoh A, Sakurai Y, Okano T, Matsumura Y, Kakizoe T, Kataoka K, J. Control. Release, 55, 219 (1998)

[28] Batrakova EV, Dorodnych TY, Klinskii EY, Kliushnenkova EN, Shemchukova OB, Goncharova ON, Arjakov SA, Alakhov VY, Kabanov AV, Br. J. Cancer, 74, 1545 (1996)

[29] Kataoka K, Pure Appl. Chem., A31, 1759 (1994)

[30] Neri P, Antoni G, Benvenuti F, Cocoda F, Gazze G, J. Med. Chem., 16, 893 (1973)

[31] Wolk SK, Swift G, Paik YH, Yocom KM, Smith RL, Simon ES, Macromolecules, 27(26), 7613 (1994)

[32] Hong SI, Kim BC, Polym.(Korea), 6(5), 336 (1982)

[33] Zhang Y, Zhuo R, Biomaterials, 26, 2089 (2005)