생분해성 Microgel로부터 약물을 담지한 Microsphere의 제조 및 그의 생분해성

김공수; 강석호; 김정묵

Journal of the Korean Industrial and Engineering Chemistry, Vol.9, No.4, 591-594, August, 1998

Export Citation

생분해성 Microgel로부터 약물을 담지한 Microsphere의 제조 및 그의 생분해성

Preparation and Biodegradability of Microsphere Prepared from Biodegradable Microgel

김공수, 강석호, 김정묵

초록

Poly(caprolactone diol)을 기초로 하여 bovine serum albumine (BSA)를 담지한 생분해성 microsphere를 용매증발법으로 제조하였다. 교반속도, microgel의 농도, 폴리비닐알콜의 농도등이 microsphere의 입도분포에 주는 영향을 조사하였다. Microsphere의 크기는 교반속도가 증가함에 따라 감소하였으나, 염화메틸렌 내의 microgel의 농도가 증가함에 따라서는 거의 비례적으로 증가하는 경향을 나타내었다. 100unit/mL의 효소용액에서 microsphere의 생분해성에 관하여 조사한 결과, 3시간이 경과한 후에 microsphere의 표면에 작은 세공들이 나타나기 시작하였으며, 24시간 후에는 세공이 발달하고 크랙이 발생하기 시작하였다. 그리고 36시간 경과한 후에는 microsphere의 구형이 일그러짐을 관찰할수 있었다.

Biodegradable microsphere containing bovine serum albumine (BSA) as a model drug were prepared with the microgel based on poly(caprolactone diol) by a modified solvent evaporation method. The influence of the stirring speed, the concentration of microgel and the mixing rate but increased with increasing the concentration of mictogel in methylene chloride. The biodegradability of microsphere in 100 unit/mL of lipase solution was investigated. A lot of small pores appeared on the surface of microsphere after 3 hours of incubation time and the pores and cracks were developed with increasing the incubation time and microsphere lost their own shape after 36 hours of incubation time.

Keywords:Microgel;Microsphere;Biodegradable Polymer;Biodegradability

[References]

Sinko P, Kohn J, "Polymeric Delivery System," ed. Magda A. El-Nokaly, David M. Piatt, 18 ~ 41, American Chemical Society, Washington, DC (1993)
Endoh H, Kawaguchi T, Seki T, Hasegawa T, Juni K, Chem. Pharm. Bull., 39, 458 (1991)
Kohjiya S, Ikeda Y, Yamashita S, Yamashita S, React. Polym., 15, 165 (1991)
Artursson P, Edman P, Laakso T, Sjoholm I, J. Pharm. Sci., 73, 1507 (1984)
Yokoyama M, Inoue S, Kataoka K, Yui N, Okano T, Sakurai Y, Makromol. Chem., 190, 2041 (1989)
Lenaerts V, Doumoulin Y, Mateescu MA, J. Control. Release, 15, 39 (1991)
Ammoury N, Fessi H, Devissaguet JP, Puisieux F, Benita S, J. Pharm. Sci., 79, 763 (1990)
Graham NB, Mao J, "Chemical Aspects of Drug Delivery System," ed. D.R. Karsa and R.A. Stephenson, 52~64, The Royal Society of Chemistry (1996)
Okawa Y, Okada H, Yamamoto M, Shimamoto T, Chem. Pharm. Bull., 36, 2576 (1988)
Nishioka Y, Kyotani S, Masui H, Okamura M, Miyazaki M, Okazaki K, Ohnishi S, Yamamoto Y, Ito K, Chem. Pharm. Bull., 37, 3074 (1989)
Seki T, Kawaguchi T, Endoh H, Ishikawa K, Juni K, Nakano M, J. Pharm. Sci., 79, 985 (1990)
Kawaguchi T, Tsugane A, Higashide K, Endoh H, Hasegawa T, Kanno H, Seki T, Juni K, Fukushima S, Nakano M, J. Pharm. Sci., 81, 508 (1992)
Hora MS, Rana RK, Nunberg JH, Tice TR, Gilley RM, Hudson ME, Pharm. Res., 7, 1190 (1990)
Jalil R, Nixon JR, J. Microencapsul., 7, 297 (1990)
Ruiz JM, Busnel jP, Benoit JP, Pharm. Res., 7, 928 (1990)
Ogawa Y, Yamamoto M, Okada H, Yashiki T, Shimamoto T, Chem. Pharm. Bull., 36, 1095 (1988)
O'Hagan DT, Jeffery H, Davis SS, Int. J. Pharm., 103, 37 (1994)
Alonso MJ, Cohen S, Park TW, Siber GR, Langer R, Pharm. Res., 10, 945 (1993)
Cohen S, Yoshioka T, Lucarelli M, Hwang HL, Langer R, Pharm. Res., 8, 713 (1991)
Kim KS, Graham NB, Polym.(Korea), to submitted (1998)
Heya T, Okada H, Tanigawara Y, Ogawa Y, Toguchi H, Int. J. Pharm., 69, 69 (1991)
Soriano I, Evora C, Llabres M, Int. J. Pharm., 142, 135 (1996)

[Referenced By]

[1] Sinko P, Kohn J, "Polymeric Delivery System," ed. Magda A. El-Nokaly, David M. Piatt, 18 ~ 41, American Chemical Society, Washington, DC (1993)

[2] Endoh H, Kawaguchi T, Seki T, Hasegawa T, Juni K, Chem. Pharm. Bull., 39, 458 (1991)

[3] Kohjiya S, Ikeda Y, Yamashita S, Yamashita S, React. Polym., 15, 165 (1991)

[4] Artursson P, Edman P, Laakso T, Sjoholm I, J. Pharm. Sci., 73, 1507 (1984)

[5] Yokoyama M, Inoue S, Kataoka K, Yui N, Okano T, Sakurai Y, Makromol. Chem., 190, 2041 (1989)

[6] Lenaerts V, Doumoulin Y, Mateescu MA, J. Control. Release, 15, 39 (1991)

[7] Ammoury N, Fessi H, Devissaguet JP, Puisieux F, Benita S, J. Pharm. Sci., 79, 763 (1990)

[8] Graham NB, Mao J, "Chemical Aspects of Drug Delivery System," ed. D.R. Karsa and R.A. Stephenson, 52~64, The Royal Society of Chemistry (1996)

[9] Okawa Y, Okada H, Yamamoto M, Shimamoto T, Chem. Pharm. Bull., 36, 2576 (1988)

[10] Nishioka Y, Kyotani S, Masui H, Okamura M, Miyazaki M, Okazaki K, Ohnishi S, Yamamoto Y, Ito K, Chem. Pharm. Bull., 37, 3074 (1989)

[11] Seki T, Kawaguchi T, Endoh H, Ishikawa K, Juni K, Nakano M, J. Pharm. Sci., 79, 985 (1990)

[12] Kawaguchi T, Tsugane A, Higashide K, Endoh H, Hasegawa T, Kanno H, Seki T, Juni K, Fukushima S, Nakano M, J. Pharm. Sci., 81, 508 (1992)

[13] Hora MS, Rana RK, Nunberg JH, Tice TR, Gilley RM, Hudson ME, Pharm. Res., 7, 1190 (1990)

[14] Jalil R, Nixon JR, J. Microencapsul., 7, 297 (1990)

[15] Ruiz JM, Busnel jP, Benoit JP, Pharm. Res., 7, 928 (1990)

[16] Ogawa Y, Yamamoto M, Okada H, Yashiki T, Shimamoto T, Chem. Pharm. Bull., 36, 1095 (1988)

[17] O'Hagan DT, Jeffery H, Davis SS, Int. J. Pharm., 103, 37 (1994)

[18] Alonso MJ, Cohen S, Park TW, Siber GR, Langer R, Pharm. Res., 10, 945 (1993)

[19] Cohen S, Yoshioka T, Lucarelli M, Hwang HL, Langer R, Pharm. Res., 8, 713 (1991)

[20] Kim KS, Graham NB, Polym.(Korea), to submitted (1998)

[21] Heya T, Okada H, Tanigawara Y, Ogawa Y, Toguchi H, Int. J. Pharm., 69, 69 (1991)

[22] Soriano I, Evora C, Llabres M, Int. J. Pharm., 142, 135 (1996)