Polymer(Korea), Vol.29, No.5, 468-474, September, 2005
단백질 전달체로서 천연 및 합성재료의 첨가에 따른 PLGA와 PCL웨이퍼로부터 알부민의 방출거동
The Release of Albumin from PLGA and PCL Wafers Containing Natural and Synthetic Additives for Protein Delivery
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초록
약물 전달체로서 캬비톨에 의해 개시된 PLGA와 PCL은 락타이드, 글라이콜라이드, 그리고 카프로락톤의 개환 중합에 의해서 합성되었다. 이들 합성고분자를 이용한 이식형 웨이퍼는 합성고분자와 모델 단백질 약물로서 소혈청알부민의 물리적 혼합 후에 성형 압축법에 의해서 간단히 제조되었다. 웨이퍼로부터 알부민의 방출량은 형광측정기를 사용하여 형광 강도에 의해서 측정되었다. 또한 웨이퍼에서 알부민의 방출거동은 콜라겐, 소장점막하조직, 폴리비닐피롤리돈, 그리고 폴리에틸렌글리콜과 같은 첨가제를 통해 조절되었다. PLGA와 PCL로만 준비된 웨이퍼에서의 알부민의 방출은 30일 동안 10% 미만의 느린 방출거동을 보였다. 그러나 첨가제를 함유한 웨이퍼는 첨가제 함량에 따라서 다양한 서빙형의 방출거동을 보였다. 더욱이 콜라겐과 소장점막하조직과 같은 천연재료를 함유한 웨이퍼는 폴리비닐피롤리돈, 폴리에틸렌글리콜과 같은 합성재료를 함유한 웨이퍼보다 0차 방출의 거동을 보였다. 이러한 이식형 웨이퍼로부터 알부민의 방출은 천연재료의 첨가를 통해 쉽게 조절할 수 있음을 확인하였다.
PLGA and PCL copolymers initiated by carbitol as drug carriers were synthesized by ring-opening polymerization of L-lactide (LA), glycolide (GA), and ε-caprolactone (ε-CL). Implantable wafers were simply fabricated by direct compression method after physical mixing of copolymers and bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) as a model protein drug. The release amounts of BSA-FITC from wafers were determined by fluorescence intensity using the fluorescence spectrophotometer. Also, the release behavior of BSA-FITC on wafers was controlled by adding the additives such as collagen, small intestinal submucosa (SIS), poly(vinyl pyrrolidone) (PVP), and poly(ethylene glycol) (PEG). The wafer prepared by PLGA and PCL exhibited slow release within 10% for 30 days. But, those prepared by a variety of additives exhibited the controlled BSA release patterns with a dependence on the additive contents. Furthermore, the wafers containing natural materials such as collagen and SIS showed more zero-order release profile than that with synthetic materials such as PVP and PEG. It was confirmed that the release of BSA from implantable wafers could be easily controlled by adding natural additives.
- Sefton MV, Biomed. Eng., 14, 201 (1987)
- Conte U, Maggi L, J. Control. Release, 64, 263 (2000)
- Lee ES, Kim SW, Cardinal JR, Jacobs H, J. Membr. Sci., 7, 293 (1980)
- Yang L, Fassihi R, J. Control. Release, 44, 135 (1997)
- Hildgen P, Mcmullen JN, J. Control. Release, 34, 263 (1995)
- Lu S, Anseth K, J. Control. Release, 57, 291 (1999)
- Lu S, Ramirez F, Anseth K, J. Pharm. Sci., 89, 45 (2000)
- Qui Y, Chidambram N, Flood K, J. Control. Release, 51, 123 (1998)
- Lewis DH, Chasin M, Biodegradable Polymers as Drug Delivery Systems, R. Langer, Editor, Marcel Dekker, Now York (1990)
- Mallarde D, Boutignon F, Moine F, Barre E, David S, Touchet H, Ferruti P, Deghenghi R, Int. J. Pharm., 261, 69 (2003)
- Cleland JL, Pharm. Biotechnol., 10, 1 (1997)
- Jain R, Rhodes CT, Railkar AM, Malick AW, Shah NH, Eur. J. Pharm. Biopharm., 50, 257 (2000)
- Zhu G, Mallery SR, Schwendeman SP, Nat. Biotechnol., 18, 52 (2000)
- Yeo Y, Park K, J. Control. Release, 100, 379 (2004)
- Berkland C, Cox A, Kim K, Pack DW, J. Biomed. Mater. Res., 70, 576 (2004)
- Jain R, Shah NH, Malick AW, Rhodes CT, Drug Dev. Ind. Pharm., 24, 703 (1998)
- Kono K, Yoshino K, Takagishi T, J. Control. Release, 80, 321 (2001)
- Lee KY, Mooney DJ, Chem. Rev., 101(7), 1869 (2001)
- Medlicott NJ, Tucker IG, Adv. Drug Deliv. Rev., 38, 139 (1999)
- Sershen S, West J, Adv. Drug Deliv. Rev., 54, 1225 (2002)
- Choi HS, Kim SW, Yun DI, Khang G, Rhee JM, Kim YS, Lee HB, Polym.(Korea), 25(3), 334 (2001)
- Seong HS, Moon DS, Khang G, Lee HB, Macromol. Chem. Symp., 4, 95 (2001)
- Choi HS, Khang G, Shin H, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002)
- An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)
- Yoo JY, Kim SW, Khang G, Seong HS, Jeong JK, Kim HJ, Lee JS, Lee HB, Polym.(Korea), 26(5), 680 (2002)
- Mergaert J, Ruffieux K, Bourban C, Storms V, Wagemans W, Wintermantel E, Swings J, J. Polym. Environ., 8, 17 (2000)
- Chen DR, Bei JZ, Wang SG, Polym. Degrad. Stabil., 67, 455 (2000)
- Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM, Chem. Rev., 99(11), 3181 (1999)
- Robert L, Science, 260, 920 (1993)
- Jeong B, Bae YH, Lee DS, Kim SW, Nature, 388(6645), 860 (1997)
- Coombes AG, Yeh MK, Lavelle EC, Davis SS, J. Control. Release, 52, 311 (1998)
- Seo KS, Park CS, Kim MS, Cho SH, Lee HB, Khang G, Polym.(Korea), 28(3), 211 (2004)
- Merrill EW, Salztman EW, J. Am. Soc. Artif. Intern, Organs, 6, 60 (1983)
- Iwata M, Ueda H, Drug Dev. Ind. Pharm., 22, 1161 (1996)
- Lamme EN, de Vries HJ, van Veen H, Gabbiani G, Westerhof W, Middelkoop E, J. Histochem. Cytochem., 44, 1311 (1996)
- Pruckmayr G, Wu TK, Macromolecules, 11, 265 (1978)
- Kim MS, Seo KS, Khang G, Lee HB, Macromol. Rapid Commun., 26, 643 (2005)