화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Korea Polymer Journal, Vol.8, No.5, 199-208, October, 2000
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Advances in Biodegradable Poymers for Drug Delivery Systems
Yong Kiel Sung†, and Sung Wan Kim1
  • Department of Chemistry, Dangguk University, Seoul 100-715, Korea
  • 1Center of Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, U.S.A., USA
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The recent development of biodegradable polymers for drug delivery system (DDS) has been investigated. The biodegradable polymers for DDS are mainly discussed in two categories: one category is natural biodegradable polymers such as polysaccharides, modified celluloses, poly(α-amino acids)s, modified proteins, and microbial biodegradable polymers; the other is synthetic biodegradable polymers such as poly(ester)s, poly(ortho ester)s, poly(phosphazene)s, poly(anhydride)s, poly(alkyl cyanoacrylate)s, and multiblock copolymers. The bioconjugate polymeric drug delivery systems have been also proposed for the design of biocompatible polymeric controlled drug delivery.
  1. Kim SW, Kopecek J, Anderson JM, Nineth International Symposium on Recent Advances in Drug Delivery Systems, CCCD, University of Utah, Salt Lake City, Utah, U.S.A. 1999 (1999)
  2. Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM, Chem. Rev., 99(11), 3181 (1999) 
  3. Domb AJ, Kost J, Wiseman DM, Handbook of Biodegradable Polymers, Harwood Academic Publishers, Netherlands, 1997 (1997)
  4. Chain M, Langer R, Biodegradable Polymers as Drug Delivery Systems, Marcel Dekker Inc., New York, 1990 (1990)
  5. Juliano RL, Drug Delivery Systems, Oxford University Press, Oxford, U.K., 1980 (1980)
  6. Kim SW, Peterson RV, Feijen J, Polymeric Drug Delivery Systems-Drug Design, J. Ariens, Ed., Academic Press, New York, 1980, Vol. 5, pp 193-215 (1980)
  7. Jeong B, Bae YH, Lee DS, Kim SW, Nature, 388(6645), 860 (1997) 
  8. Langer R, Science, 249, 1527 (1990) 
  9. Park K, Shalaby WSW, Park H, Biodegradable Hydrogels for Drug Delivery, Technomic Publishing Co. Inc., Lancaster, Pennsylvania, 1993 (1993)
  10. Ottenbrite RM, Huang SJ, Park K, Hydrogels and Biodegradable Polymers for Bioapplications, ACS Symposium Series 627, American Chemical Society, Washington, D.C., 1994 (1994)
  11. Kang IK, Kwon DR, Sung YK, Polym.(Korea), 15(4), 481 (1991)
  12. Kim JH, Kim JY, Lee YM, Kim KY, Cho CS, Sung YK, Polym.(Korea), 15(6), 695 (1991)
  13. Sung YK, Ha JH, Kim SH, Han SY, Cho CS, J. Control. Release, 49, 253 (1997) 
  14. Dickinson HR, Hiltner A, Gibbons DF, Anderson JM, J. Biomed. Mater. Res., 15, 577 (1981) 
  15. Dickinson HR, Hiltner A, J. Biomed. Mater. Res., 15, 590 (1981)
  16. Okada H, Yamamoto M, Heya T, Inoue Y, Kamei K, Ogawa Y, Toguchi H, J. Control. Release, 28, 121 (1994) 
  17. Sanders LM. McRac GI, Vitale KM, Kell BA, J. Control. Release, 12, 187 (1985)
  18. Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Black NA, Sisti M, Brem S, Mohr G, Lancet, 345, 1008 (1995) 
  19. Brem H, Walter KA, Tamargo RJ, Olivi A, Langer R, Drug Delivery to the Brain, in Polymeric Site Specific Pharmacotheraphy, A. Domb, Ed., Wiley, New York, 1994, pp 117-140
  20. Seo MH, Kim CS, Kim DW, Shim YH, Kim SW, Oh JH, J. Control. Release, in press (2000)
  21. Maheshwari A, Mahato RI, McGregor J, Han S, Samlowski WE, Park J, Kim SW, Molecular Therapy, 2(2) (2000)
  22. Kost J, Goldbalt R, Natural and Modified Polysaccharides, in Handbook of Biodegradable Polymers, A.J. Domb, J. Kost, and D.M. Wiseman, Eds., 1997, Chap. 14, pp 275-289 (1997)
  23. Shalby WSW, Park K, Chemical Modification of Proteins and Polysaccharides and Its Effect on Enzyme-Catalyzed Degradation, in Biomedical Polymers, W.S.W. Shalby, Ed., Hanser International, Munchen, Germany, 1994 (1994)
  24. Vandenbossche G, Leffebvre R, De Wilde G, Remon JP, J. Pharm. Sci., 81, 245 (1992) 
  25. Laakso T, Sjoholm I, J. Pharm. Sci., 76, 935 (1987)
  26. Laakso T, Artursson P, Sjoolm I, J. Pharm. Sci., 75, 962 (1986) 
  27. Stjarnkvist P, Degling L, Sjoholm I, J. Pharm. Sci., 80, 436 (1991) 
  28. Stjarnkvist P, Laakso T, Sjoholm I, J. Pharm. Sci., 78, 52 (1989) 
  29. Johansson CJ, Clin. Pharmacokinet., 31, 231 (1996)
  30. Artursson P, Edman P, Sjoholm I, J. Pharmacol. Exp. Ther., 231, 705 (1984)
  31. Kost J, Shefer S, Biomaterials, 11, 695 (1990) 
  32. Crepon B, Jozefonvicz J, Chytry V, Rihova B, Kopecek J, Biomaterials, 12, 550 (1991) 
  33. Subr V, Duncan R, Kopecek J, J. Biomater. Sci.-Polym. Ed., 1(4), 261 (1990)
  34. Harbae E, Larsen C, Johansen M, Olesen HP, Pharm. Res., 6, 919 (1989) 
  35. Edman P, Ekman B, Sjoholm I, J. Pharm. Sci., 69, 838 (1980) 
  36. Pangburn SH, Trescony PV, Heller J, Biomaterials, 3(2), 105 (1982) 
  37. Itoyama K, Tokura S, Hayashi T, Biotechnol. Prog., 10(2), 225 (1994) 
  38. Kim SJ, Lee YM, Sung YK, Kang IK, Park YH, J. Korean Ind. Eng. Chem., 4(4), 785 (1993)
  39. Hirano S, Tsuchida H, Nagao N, Biomaterials, 10, 574 (1989) 
  40. Bindschaedler C, Gurney R, Doclker E, J. Pharm. Pharmacol., 39, 335 (1987)
  41. Stilwell RL, Marks MG, Saferstein L, Wiseman DM, Oxidized Cellulose, in Handbook of Biodegradable Polymers, A.J. Domb, J. Kost, and D.M. Wiseman, Eds., Harwood Academic Publishers, U.K., 1997, Chap. 15, pp 291-306 (1997)
  42. Scher KS, Coil JA, Surgery, 91, 301 (1982)
  43. Dineen P, J. Surg. Res., 23, 114 (1977) 
  44. Dineen P, Surg. Gynecol. Obstet., 142, 481 (1976)
  45. Reid RL, Lie K, Spence JE, Tulandi T, Yuzpe A, Prog. Clin. Biol. Res., 381, 261 (1993)
  46. Wiseman DM, Kamp L, Linsky CB, Jochen RF, Pang RH, Scholz PM, J. Surg. Res., 53, 362 (1992) 
  47. Bindschaedler C, Gurny R, Doelker E, J. Pharm. Pharmacol., 39, 335 (1987)
  48. Tovey ER, Ford SA, Baldo BA, J. Biochem. Biophys. Methods, 14, 1 (1987) 
  49. Ford JL, Rubinstein MH, McCaul F, Hogan JE, Edgar P, Int. J. Pharm., 40, 223 (1987) 
  50. Katchalsky E, Sela M, Protein Chem., 13, 243 (1958)
  51. Anderson JM, Fang SM, Feijen J, Gregonis D, Kim SW, Polym. Preprints, 20, 20 (1979)
  52. Negishi A, Bennett DB, Jeong SY, van Heewijk W, Feijen J, Kim SW, Pharm. Res., 4, 305 (1987) 
  53. Bennett DB, Li X, Adams NW, Hoes CJT, Feijen J, Kim SW, J. Control. Release, 22, 181 (1992) 
  54. Lemieux P, Vinogradov SV, Gebhart CL, Guerin N, Paradis G, Nguyen HK, Ochietti B, Suzdaltseva YG, Bartakova EV, Bronich TK, St-Pierre Y, Alakhov VY, Kabanov AV, J. Drug Target., 8, 91 (2000)
  55. Charlier A, Leclerc B, Couarraze G, Int. J. Pharm., 200, 115 (2000) 
  56. Bentolila A, Vlodavsky I, Ishai-Michaeli R, Kovalchuk O, Haloun C, Domb AJ, J. Med. Chem., 43, 2591 (2000) 
  57. Kwon HY, Langer R, Macromolecules, 22, 3250 (1989) 
  58. Kohn J, Drugs Pharm. Sci., 45, 195 (1990)
  59. Pulapula S, Li C, Kohn J, Biomaterials, 11, 666 (1990) 
  60. Kim BS, Hrkach JS, Langer R, Biomaterials, 21, 259 (2000) 
  61. Yoshida M, Asano M, Kumakura M, Katakai R, Mashima T, Yuasa H, Imai K, Yamanaka H, J. Biomed. Mater. Res., 24, 1173 (1990) 
  62. Helder J, Ph.D. Thesis, Twente University of Technology (1988)
  63. Anderson JM, Gibbons DF, Martin RL, Hiltner A, Woods R, J. Biomed. Mater. Res. Symp., 5, 197 (1974)
  64. Helder J, Dijkstra J, Feijen J, J. Biomed. Mater. Res., 24, 1005 (1990) 
  65. Asano M, Yoshida M, Kaetsu I, Katakai R, Mashimo T, Yuasa H, Imai K, Yamanaka K, Polym. J., 20, 281 (1988) 
  66. Myers JC, Yang H, DIppolito A, Presente A, Miller MK, Dion AS, J. Biol. Chem., 269, 18549 (1994)
  67. van der Rest M, Bruckner P, Current Opinion Structural Biology, 3, 430 (1993) 
  68. Prockop DJ, N. Engl. J. Med., 326, 540 (1992)
  69. Trubetskoy VS, Budker VG, Hanson LJ, Slattum PM, Wolff JA, Hagstrom JE, Nucleic Acids Res., 26, 4178 (1998) 
  70. Muller BG, Leuenberger H, Kissel T, Pharm. Res., 13, 32 (1996) 
  71. Doughty JC, Anderson JH, Willmott N, McArdle CS, Postgrad. Med. J., 71, 47 (1995)
  72. Cheng YH, Liao GT, Hou SX, Li L, Zhang M, Yao Hsueh Hsueh Pao, 28, 68 (1993)
  73. Verrijk R, Smolders IJ, McVie JG, Begg AC, Cancer Chemother. Pharmacol., 29, 117 (1991) 
  74. Davis SS, Hunneyball IM, Illum L, Rateliffe JH, Smith A, Wilson CG, Drugs Exp. Clin. Res., 11, 633 (1985)
  75. Bosela AA, El-Sayed MM, Mahmoud MI, Boll. Chim. Farm., 137, 77 (1998)
  76. Iseri E, Ercan MT, Kas HS, Hincal AA, Boll. Chim. Farm., 130, 66 (1991)
  77. Yan CH, Li XW, Chen XL, Wang DQ, Zhong DC, Tan TZ, Kitano H, Biomaterials, 12, 640 (1991) 
  78. Rao JK, Ramesh DV, Rao KP, J. Biomater. Sci.-Polym. Ed., 6, 391 (1994)
  79. Yasukawa T, Kimura H, Tanaba Y, Miyamoto H, Honda Y, Ikada Y, Ogura Y, Invest. Opthalmol. Vis. Sci., 40, 2690 (1999)
  80. Zhang Z, Lu B, Shu G, Xie H, Yi Q, He Y, Wang J, Hua His Ko Ta Hsueh Hsueh Pao., 26, 167 (1995)
  81. Wang JH, Lu B, Xu PL, Bao DY, Zhang ZR, Yao Hsueh Hsueh Pao., 30, 549 (1995)
  82. Chowdhury DK, Mitra AK, Int. J. Pharm., 193, 113 (1999) 
  83. Herrmann R, Schmidmaier G, Markl B, Resch A, Hahnel I, Stemberger A, Alt E, Thromb. Haemost., 82, 51 (1999)
  84. Schakenraad JM, Oosterbaan JA, Nieuwenhuis P, Molenaar I, Olijslager J, Potman W, Eenink MJ, Feijen J, Biomaterials, 9, 116 (1988) 
  85. Hasty B, Heuer DK, Minckler DS, Am. J. Ophthalmology, 109, 721 (1990)
  86. Hwang DG, Stern WH, Hwang PH, MacGowan-Smith LA, Archives Ophthalmology, 107, 1375 (1989)
  87. Chen YE, Gebhardt B, McReidy JJ, Kaufman HE, Am. J. Ophthalmology, 109, 132 (1990)
  88. Kopecek J, Biomaterials, 5, 19 (1984) 
  89. Brondsted H, Kopecek J, Pharm. Res., 9, 1540 (1992) 
  90. Saffran M, Kumar GS, Savariar C, Burnham JC, Williams F, Neckers DC, Science, 233, 1081 (1986) 
  91. Gilding DK, Reed AM, Polymer, 20, 1459 (1979) 
  92. Mooney DJ, Organ G, Vacanti JP, Langer R, Cell Transpl., 2, 203 (1994)
  93. Lewis DH, Biodegradable Polymers as Drug Delivery Systems, M. Chasin and R. Langer, Eds., Marcel Dekker, New York, 1990, pp 1-15 (1990)
  94. Shin GI, Kim JH, Kim SH, Kim YH, Korea Polym. J., 5(1), 19 (1997)
  95. Lee JS, Choo DJ, Kim SH, Kim YH, Polym.(Korea), 22(6), 880 (1998)
  96. Okada H, Yamamoto M, Heya T, Inoue Y, Kamei K, Ogawa Y, Touchi H, J. Control. Release, 28, 121 (1994) 
  97. Heya T, Okada H, Ogawa Y, Touchi H, Int. J. Pharm., 72, 199 (1991) 
  98. Mestecky J, Moldoveanu Z, Novak N, Huang WQ, Gilly RM, Stags JK, Schafer D, Coupans RW, J. Control. Release, 28, 131 (1994) 
  99. Heller J, Handbook of Biodegradable Polymers, A.J. Domb, J. Kost, and D.M. Wiseman, Eds., Harwood Academic Publishers, U.K., 1997, pp 99-118 (1997)
  100. Choi NS, Heller J, U.S. Patent, 4,079,038 (1978)
  101. Choi NS, Heller J, U.S. Patent, 4,093,709 (1978)
  102. Choi NS, Heller J, U.S. Patent, 4,131,648 (1978)
  103. Choi NS, Heller J, U.S. Patent, 4,138,344 (1979)
  104. Choi NS, Heller J, U.S. Patent, 4,180,646 (1979)
  105. Capozza RC, Sendelbeck SL, Balkenhol WJ, PolymericDelivery Systems, R.J. Kostelnik, Ed., Gordon and Breach, New York, 1978, pp 59-76 (1978)
  106. Heller J, Ng SY, Penhale DW, Fritzinger BK, Sanders LM, Burns RA, Gaynon MG, Bhosale SS, J. Control. Release, 6, 217 (1987) 
  107. Heller J, Penhale DW, Helwing RF, J. Polym. Sci. C-Polym. Lett., 18, 619 (1980)
  108. Ng SY, Penhale DW, Heller J, Macromol. Synth., 11, 23 (1992)
  109. Seymour LW, Duncan R, Duffy J, Ng SY, Heller J, J. Control. Release, 31, 201 (1994) 
  110. Maa YF, Heller J, J. Control. Release, 14, 21 (1990) 
  111. Heller J, Adv. Polym. Sci., 107, 43 (1993)
  112. Heller J, Fritzinger BK, Ng SY, Penhale DW, J. Control. Release, 1, 233 (1985) 
  113. Heller J, Chang AC, Rodd G, Grodsky GM, J. Control. Release, 13, 295 (1990) 
  114. Heller J, Ng SY, Fritzinger BK, Roskos KV, Biomaterials, 11, 235 (1990) 
  115. Roskos KV, Fritzinger BK, Rao SS, Armitage GC, Heller J, Biomaterials, 16, 313 (1995) 
  116. Wuthrich P, Ng SY, Fritzinger BK, Roskos KV, Heller J, J. Control. Release, 21, 191 (1992) 
  117. Heller J, Ng SY, Fritzinger BK, Macromolecules, 25, 3362 (1992) 
  118. Allcock HR, Chem. Rev., 72, 315 (1972) 
  119. Allcock HR, Makromol. Chem. Macromol. Symp., 6, 101 (1986)
  120. Allcock HR, Biomaterials, 13, 857 (1992) 
  121. Allcock HR, Biodegradable Polymers as Drug Delivery Systems, R. Langer, and M. Chasin, Eds., M. Dekker, New York, 1990, pp 163-193 (1990)
  122. Laurencin CT, Koh HJ, Neenan TX, Allcock HR, Langer R, J. Biomed. Mater. Res., 21, 1231 (1987) 
  123. Allcock HR, Oconnor SJ, Olmeijer DL, Napierala ME, Cameron CG, Macromolecules, 29(23), 7544 (1996) 
  124. Allcock HR, Ambrosio A, Polym. Preprints, 41, 732 (2000)
  125. Allcock HR, Pucher SR, Scopelianos AG, Biomaterials, 15, 563 (1994) 
  126. Allcock HR, Dudley GK, Macromolecules, 29(4), 1313 (1996) 
  127. Allcock HR, Fuller TJ, Matsumura K, Inorg. Chem., 21, 515 (1982) 
  128. Cohen S, Bano MC, Visscher KB, Chow M, Allcock HR, Langer R, J. Am. Chem. Soc., 112, 7832 (1990) 
  129. Leong KW, Brott BC, Langer R, J. Biomed. Mater. Res., 19, 941 (1985) 
  130. Domb AJ, Langer R, J. Polym. Sci. A: Polym. Chem., 25, 373 (1987) 
  131. Leong KW, Simonte V, Langer R, Macromolecules, 20, 705 (1987) 
  132. Domb AJ, Ron E, Langer R, Macromolecules, 21, 1925 (1988) 
  133. Domb AJ, Gallardo CE, Langer R, Macromolecules, 22, 3200 (1989) 
  134. Domb AJ, Biomaterials, 11, 680 (1990)
  135. Albertsson A, Lundmark S, J. Macromol. Sci.-Chem., A22, 23 (1990)
  136. Laurencin C, Gerhart T, Witschger P, Satcher R, Domb AJ, Hanff P, Edsberg L, Hayes W, Langer R, J. Orthop. Res., 11, 256 (1993) 
  137. Domb AJ, Ringel I, Providing Pharmaceutical Access to the Brain, Methods in Neuro-science, T.R. Flanaga, D.F. Emerich, and S.R. Winn, Eds., CRC press, 1999, Vol. 21, pp 169-183 (1999)
  138. Laurencin CT, Ibim SE, Langer R, Biomedical Applications of Synthetic Biodegradable Polymers, J.O. Hollinger, Ed., CRC Press, Boca Raton, 1995, pp 59-102 (1995)
  139. Domb AJ, Nudelman R, Biomaterials, 16, 319 (1995) 
  140. Pepper DC, Makromol. Chem. Macromol. Symp., 60, 267 (1992)
  141. Pepper DC, J. Polym. Sci., 62, 65 (1978)
  142. Alvotidinov A, Dokl. Akad. Nauk. Uzb. USSR, 7, 41 (1982)
  143. Leonard F, Kurkarni RA, Brandes G, Nelson J, Cameron JJ, J. Appl. Polym. Sci., 10, 259 (1966) 
  144. Kopecek J, Ulbrich K, Prog. Polym. Sci., 9, 1 (1983) 
  145. Vezin WR, Florence AT, J. Biomed. Mater. Res., 14, 93 (1980) 
  146. Hegyeli AF, J. Biomed. Mater. Res., 7, 205 (1973)
  147. Kattan J, Droz JP, Couvreur P, Marino JP, Boutan-Laroze A, Rougier P, Brault P, Vranckx H, Grognet JM, Morge X, Sancho-Garnier L, Invest. New Drugs, 10, 191 (1992) 
  148. Muller RH, Lherm C, Herbort J, Couvreur P, Biomaterials, 11, 590 (1990) 
  149. Verdun C, Brasseur F, Vranckx H, Couvreur P, Roland M, Cancer Chemother. Pharmacol., 26, 13 (1990) 
  150. Maincent P, Devissaguet JP, LeVerge R, Sado PA, Couvreur P, Appl. Biochem. Biotechnol., 10, 263 (1984)
  151. Zhu KJ, Lin X, Yang S, J. Appl. Polym. Sci., 39, 1 (1990) 
  152. Ronneberger B, Kao WJ, Anderson JA, Kissel T, J. Biomed. Mater. Res., 30, 31 (1996) 
  153. Jeong B, Bae YH, Lee DS, Kim SW, Nature, 388(6645), 860 (1997) 
  154. Jeong B, Choi YK, Bae YH, Zentner G, Kim SW, J. Control. Release, 62, 109 (1999) 
  155. Tang MX, Redemann CT, Szoka FC, Bioconjug. Chem., 7, 703 (1996) 
  156. Jeong B, Bae YH, Kim SW, J. Control. Release, 63, 155 (2000) 
  157. Jeong B, Bae YH, Kim SW, World Biomater. Cong. Trans., 3, 1941 (2000)
  158. Yeh PY, Kopeckova P, Kopecke P, Macromol. Chem. Phys., 196, 2183 (1995) 
  159. Ghandehari H, Kopeckova P, Yeh PY, Kopecek P, Macromol. Chem. Phys., 197, 965 (1996) 
  160. Putnam D, Kopecek P, Bioconjug. Chem., 6, 483 (1995) 
  161. Kamei S, Kopecek P, Pharm. Res., 12, 663 (1995) 
  162. Minko T, Kopeckova P, Kopecek P, J. Control. Release, 59, 133 (1999) 
  163. Wang D, Kopeckova P, Minko T, Nanayakkara V, Kopecek P, Polym. Preprints, 41, 994 (2000)
  164. Yasugi K, Nakasaki Y, Kao M, Kataoka K, J. Control. Release, 62, 89 (1999) 
  165. Katayose S, Kataoka K, J. Pharm. Sci., 87, 160 (1998) 
  166. Harada A, Kataoka K, Science, 283, 65 (1999) 
  167. Suh H, Jeong B, Rathi R, Kim SW, J. Biomed. Mater. Res., 42, 331 (1998) 
  168. Grijpma DW, Feijen J, J. Control. Release, in press (2000)
  169. Lim Y, Han S, Kong H, Lee Y, Park J, Jeong B, Kim SW, Pharm. Res., 17, 811 (2000)