Preparation and Characterizaion of Gentamicin Sulfate Loaded Poly(L-lactic-co-glycolide) Microspheres for the Treatment of Osteomyelitis

Jin Cheol Cho; Gilson Khang; John M. Rhee; Yong Sik Kim; Jung Sik Lee; Hai Bang Lee

Korea Polymer Journal, Vol.7, No.2, 79-85, April, 1999

Jin Cheol Cho, Gilson Khang , John M. Rhee , Yong Sik Kim¹, Jung Sik Lee², and Hai Bang Lee^{3, †}

Department of Polymer Science and Technology, Chonbuk National University, Dukjin, Chonju 561-756, Korea
¹Department of Orthopedic Surgery, Catholic Medical School, Youido-dong, Youngdeungpo. Seoul 150-010, Korea
²Research Center, Samchundang Pharm. Co. Ltd., P.O. Box 289, Youngdeungpo, Seoul 150-037, Korea
³Biomaterials Laboratory, Korea Research Institute of Chemical Technology, P.O.Box 107, Yusung, Taejon 305-606, Korea

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Controlled gentamicin sulfate(GS) releasing microspheres manufactured from biodegradable poly(L-lactide-co-glycolide)(PLGA, 75:25 by mole ratio) were prepared with an oil/oil solvent evaporation method for the treatment of osteomyelitis. The microspheres of different size (30∼350㎛)were obtained with varying the experimental conditions, and the shape of microspheres was smooth and spherical. The efficiency of encapsulation was over 81%. The effects of the preparation conditions on the size of microspheres have been investigated. In vitro release studies showed that different release patterns and release rates could be achieved by simply modifying factors in the preparation conditions such as polymer concentration, surfactant concentration, molecular weight of PLGA and initial amount of loaded drug. PLGA microspheres with 20% of initial drug loading, 0.2%(w/w) of surfactant concentration and 50% (w/v) of PLGA concentration, were free from initial burst effect and a near-zero order sustained release was observed for over 60 days. Mechanisms of the prolonged sustained release from the larger GS/PLGA microspheres with over 100㎛ medium size have been proposed.

[References]

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Mauduit J, Buhk N, Vert M, J. Control. Release, 23, 209 (1993)
Wahlig H, Dingeldein E, Bergmann R, Reuss K, J. Bone Joint Surgery, 60-B, 270 (1978)
Robinson DH, Sampath SS, Drug Dev. Ind. Pharm., 15, 2339 (1989)
Trippel SB, J. Bone Joint Surg., 68A, 1297 (1986)
Ikada Y, Hyon SH, Jamshidi K, Higashi S, Yamamuro T, Katutani Y, Kitsugi T, J. Control. Release, 2, 179 (1985)
Yamamura K, Iwata H, Yotsuyanagi T, J. Biomed. Mater. Res., 26, 1053 (1992)
Sampath SS, Garvin K, Robinson DH, J. Pharm., 78, 165 (1992)
Setterstrom JA, Tice TR, Meyers WE, Vincent JW, Battisone GC, Polym. Mater. Eng., 53, 620 (1985)
Shinto Y, Uchida A, Korkusuz F, Araki M, Ono K, J. Bone Joint Surg., 74B, 600 (1992)
Yu D, Wong J, Matsuda Y, Fox JL, Higuchi WI, Otsuka M, J. Pharm. Sci., 65, 1563 (1992)
Firsov AA, Navarov AD, Fomina IP, Drug Dev. Ind. Pharm., 13, 1651 (1987)
Zhang X, Wyss P, Pichora D, Goosen MFA, J. Macromol. Sci.-Macromol. Chem., A30, 933 (1993)
Wei G, Kotoura Y, Oka M, Yamamuro T, Wada R, Hyon SH, Ikada Y, J. Bone Joint Surg., 73B, 246 (1990)
Gilding DK, Reed AM, Polymer, 20, 1459 (1970)
Beck LR, Cowsar DR, Lewis DH, Cosgrove RJ, Lowry SL, Epperly T, Fertil. Steril., 31, 545 (1979)
Schmidt C, Wenz R, Nies B, Moll F, J. Control. Release, 37, 83 (1995)
Wakiyama N, Juni K, Nakano M, Chem. Pharm. Bull., 11, 3363 (1981)
Mandal TK, Tenjarla S, Int. J. Pharm., 137, 187 (1996)
Jalil R, Nixon JR, J. Microencapsul., 7, 25 (1990)
Jalil R, Nixon JR, J. Microencapsul., 7, 41 (1990)
Mandal TK, J. Pharm. Sci., 2, 99 (1996)
Jalil R, Nixon JR, J. Microencapsul., 7, 53 (1990)
Suzuki K, Price JC, J. Pharm. Sci., 74, 21 (1985)
Ogawa Y, Yamamoto M, Okada H, Yashiki T, Shimamoto T, Chem. Pharm. Bull., 36, 1095 (1998)
Yeh MK, Coombes AGA, Jenkins PG, Davis SS, J. Control. Release, 33, 437 (1995)
Yan C, Resau JH, Heweton J, West M, Rill WL, Kende M, J. Control. Release, 32, 231 (1994)
Iwata M, McGinity JW, Pharm. Res., 10, 1219 (1993)
Wada R, Hyon SH, Ikada Y, J. Pharm. Sci., 79, 919 (1990)
Kyo M, Hyon SH, Ikada Y, J. Control. Release, 35, 73 (1995)
Khang G, Cho JC, Lee JW, Rhee JM, Lee HB, Bio-Med. Mater. Eng., in press, 9 (1999)
USP, NF, 702 (1995)
Sansdrap P, Moes AJ, Int. J. Pharm., 98, 157 (1993)
George C, Park TG, J. Control. Release, 35, 91 (1995)
Sturesson C, Carlfors J, Edman K, Andersson M, Int. J. Pharm., 89, 235 (1993)
Ogawa Y, Yamamoto M, Okada H, Yashiki T, Yamamoto T, Chem. Pharm. Bull., 36, 1294 (1984)

[Referenced By]

[Related Articles]

[1] Klemm K, Septopal a new way of local antibiotic therapy. In T.J.G. van Rens, and F.H. Keyser Eds., Local Antibiotic Treatment in Osteomyelitis and Soft Tissue Infections, Excerpta Medica, Amsterdam, 24 (1981)

[2] Mauduit J, Buhk N, Vert M, J. Control. Release, 23, 209 (1993)

[3] Wahlig H, Dingeldein E, Bergmann R, Reuss K, J. Bone Joint Surgery, 60-B, 270 (1978)

[4] Robinson DH, Sampath SS, Drug Dev. Ind. Pharm., 15, 2339 (1989)

[5] Trippel SB, J. Bone Joint Surg., 68A, 1297 (1986)

[6] Ikada Y, Hyon SH, Jamshidi K, Higashi S, Yamamuro T, Katutani Y, Kitsugi T, J. Control. Release, 2, 179 (1985)

[7] Yamamura K, Iwata H, Yotsuyanagi T, J. Biomed. Mater. Res., 26, 1053 (1992)

[8] Sampath SS, Garvin K, Robinson DH, J. Pharm., 78, 165 (1992)

[9] Setterstrom JA, Tice TR, Meyers WE, Vincent JW, Battisone GC, Polym. Mater. Eng., 53, 620 (1985)

[10] Shinto Y, Uchida A, Korkusuz F, Araki M, Ono K, J. Bone Joint Surg., 74B, 600 (1992)

[11] Yu D, Wong J, Matsuda Y, Fox JL, Higuchi WI, Otsuka M, J. Pharm. Sci., 65, 1563 (1992)

[12] Firsov AA, Navarov AD, Fomina IP, Drug Dev. Ind. Pharm., 13, 1651 (1987)

[13] Zhang X, Wyss P, Pichora D, Goosen MFA, J. Macromol. Sci.-Macromol. Chem., A30, 933 (1993)

[14] Wei G, Kotoura Y, Oka M, Yamamuro T, Wada R, Hyon SH, Ikada Y, J. Bone Joint Surg., 73B, 246 (1990)

[15] Gilding DK, Reed AM, Polymer, 20, 1459 (1970)

[16] Beck LR, Cowsar DR, Lewis DH, Cosgrove RJ, Lowry SL, Epperly T, Fertil. Steril., 31, 545 (1979)

[17] Schmidt C, Wenz R, Nies B, Moll F, J. Control. Release, 37, 83 (1995)

[18] Wakiyama N, Juni K, Nakano M, Chem. Pharm. Bull., 11, 3363 (1981)

[19] Mandal TK, Tenjarla S, Int. J. Pharm., 137, 187 (1996)

[20] Jalil R, Nixon JR, J. Microencapsul., 7, 25 (1990)

[21] Jalil R, Nixon JR, J. Microencapsul., 7, 41 (1990)

[22] Mandal TK, J. Pharm. Sci., 2, 99 (1996)

[23] Jalil R, Nixon JR, J. Microencapsul., 7, 53 (1990)

[24] Suzuki K, Price JC, J. Pharm. Sci., 74, 21 (1985)

[25] Ogawa Y, Yamamoto M, Okada H, Yashiki T, Shimamoto T, Chem. Pharm. Bull., 36, 1095 (1998)

[26] Yeh MK, Coombes AGA, Jenkins PG, Davis SS, J. Control. Release, 33, 437 (1995)

[27] Yan C, Resau JH, Heweton J, West M, Rill WL, Kende M, J. Control. Release, 32, 231 (1994)

[28] Iwata M, McGinity JW, Pharm. Res., 10, 1219 (1993)

[29] Wada R, Hyon SH, Ikada Y, J. Pharm. Sci., 79, 919 (1990)

[30] Kyo M, Hyon SH, Ikada Y, J. Control. Release, 35, 73 (1995)

[31] Khang G, Cho JC, Lee JW, Rhee JM, Lee HB, Bio-Med. Mater. Eng., in press, 9 (1999)

[32] USP, NF, 702 (1995)

[33] Sansdrap P, Moes AJ, Int. J. Pharm., 98, 157 (1993)

[34] George C, Park TG, J. Control. Release, 35, 91 (1995)

[35] Sturesson C, Carlfors J, Edman K, Andersson M, Int. J. Pharm., 89, 235 (1993)

[36] Ogawa Y, Yamamoto M, Okada H, Yashiki T, Yamamoto T, Chem. Pharm. Bull., 36, 1294 (1984)