Polymer(Korea), Vol.27, No.4, 370-376, July, 2003
PEG-PPG 블록 공중합체를 이용한 폴리(DL-락타이드-co-글리콜라이드) 나노입자의 제조
Preparation of Poly(DL-lactide-co-glycolide) Nanoparticles by PEG-PPG Diblock Copolymer
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초록
나노입자의 제조 방법인 개선된 자발적 용매 확산 방법을 이용하여 폴리(DL-락타이드-co-글리콜라이드) 나노입자를 제조하였다. 고분자 용액은 물에 잘 혼합되는 유기 용매인 에탄올과 아세톤의 이종 혼합 용매를 사용하여 제조하였다. 유화제 및 안정제는 우수한 생체적합성을 갖는 PEG-PPG 블록 공중합체를 사용하였다. 최적의 나노입자 제조 조건을 얻기 위하여 나노입자 형성에 영향을 주는 인자들인 안정제의 종류 및 농도, 교반 방법, 물/오일 상의 비, 고분자의 농도 등을 고려하였다. 나노입자 제조 후, 입자의 크기 및 분산도는 광산란 입도 분석기를 이용하여 평가하였다. 제조된 나노입자는 50 ~ 200 nm의 크기와 단분산 형태의 크기분포를 보였다. 또한, 유기상과 수용액상에서 이종 혼합 용매와 고분자의 농도에 대한 적당한 조건을 조절함으로써 PLGA 나노입자의 높은 수율과 우수한 물리적 특성을 얻을 수 있었다.
Poly(DL-lactide-co-glycolide) nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method. Polymer solution was prepared by two water-soluble organic solvents, such as ethanol and acetone. Because of its biocompatible nature, PEG-PPG diblock copolymer was used as surfactant and stabilizer. The influence of several preparative variables on the nanoparticle formation, such as type and concentration of stabilizing agent, stirring methods, water/oil phase ratio and polymer concentration were investigated in order to control and optimize the process. After preparation of nanoparticles, particle size and distribution were evaluated by the light scattering particle analyzer. As results, the particle size was 50-200 nm and dispersibility was monodisperse. It was found that the appropriate selections of binary solvent mixtures and polymeric concentrations in both organic and aqueous phases could provide a good yield and favorable physical properties of PLGA nanoparticles.
- Lewis DH, Chasim M, Biodegradable Polymer as Drug Delivery Systems, Marcel Dekker, New York (1990)
- Alexakis T, Boadi DK, Quong D, Groboillot A, Oneill I, Poncelet D, Neufeld RJ, Appl. Biochem. Biotechnol., 50(1), 93 (1995)
- Lu W, Park TG, J. Pharm. Sci. Technol., 45, 13 (1995)
- Kim A, Park SJ, Lee JR, J. Colloid Interface Sci., 197(1), 119 (1998)
- Jeong YI, Shim YH, Song KC, Park YG, Ryn HW, Nah JW, Bull. Korean Chem. Soc., 23, 1579 (2002)
- Jeong YI, Ryn JG, Kim YH, Kim SH, Bull. Korean Chem. Soc., 23, 872 (2002)
- Park SJ, Kim SH, Lee JR, Lee HB, Hong SK, Polym.(Korea), 26(3), 326 (2002)
- Khang G, Seo SA, Choi HS, Rhee JM, Lee HB, Macromol. Res., 10(5), 246 (2002)
- Cho JC, Khang G, Rhee JM, Kim YS, Lee JS, Lee HB, Korea Polym. J., 7(2), 79 (1999)
- Khang G, Lee JH, Lee JW, Cho JC, Lee HB, Korea Polym. J., 8(2), 80 (2000)
- Kweon JK, Jeong YI, Jang MK, Lee CH, Nah JW, Polym.(Korea), 26(4), 535 (2002)
- Govender T, Stolik S, Garnett MC, Illum L, Davis SS, J. Control. Release, 57, 171 (1999)
- Cho JC, Khang G, Choi HS, Rhee JM, Lee HB, Polym.(Korea), 24(5), 728 (2000)
- Fessi H, Ammoury PN, Benita S, Int. J. Pharm., 55(1), R1 (1989)
- Omelozuk MO, Mcginity JW, STP Pharm. Sci., 5, 181 (1995)
- Holland SJ, Tighe BJ, Gould PL, J. Control. Release, 4, 155 (1986)
- Gurny R, Peppas NA, Harrington DD, Banker GS, Drug Dev. Ind. Pharm., 7, 1 (1981)
- Allemann E, Gurny R, Doelker E, Int. J. Pharm., 87, 247 (1992)
- Choi SW, Kwon HY, Kim WS, Kim JH, Colloids Surf., 201, 283 (2002)
- Quintanar-Guerrero D, Fessi H, Allemann E, Doelker E, Int. J. Pharm., 143, 133 (1996)
- Niwa T, Takeuchi H, Hino T, Kunou N, Kawashima Y, J. Control. Release, 25, 89 (1993)
- Schada A, Niwa T, Takeuchi H, Hino T, Kawashima Y, Int. J. Pharm., 117, 209 (1995)
- Murakami H, Kawashima Y, Niwa T, Hino T, Takeuchi H, Kobayashi H, Int. J. Pharm., 149, 43 (1997)
- Murakami H, kobayashi M, Takeuchi H, Kawashima Y, Int. J. Pharm., 187, 143 (1999)
- Murakami H, Kobayashi M, Takeuchi H, Kawashima Y, Powder Technol., 107(1-2), 137 (2000)
- Gupta PK, Pharm. Sci., 79, 949 (1992)
- Murakami H, Kawashima Y, Niwa T, Hino T, Takeuchi H, Kobayashi M, Int. J. Pharm., 149, 43 (1997)