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Intracellular Delivery of Drugs to Macrophages

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Biotechnology in India I

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 84))

Abstract

Toxic side effects which often complicate successful therapy in a number of diseases possibly arise due to the fact that at therapeutically effective concentrations the non-target cells in the body are also exposed to the cytotoxic effects of the drugs. Minimization of such adverse reactions might be feasible through drug delivery modalities that would reduce the uptake of the drugs by non-target cells and selectively deliver the drug only to the target cells (and/or intracellular sites) at relatively low extracellular concentrations. The current generic approach to site-specific drug delivery consists of attaching the therapeutic agent to a carrier recognized only by the cells where the pharmacological action is desired. Two types of recognition elements on the surface of target cells are being exploited for this purpose, viz., (i) antigens capable of generating specific, non-cross reactive antibodies, and (ii) receptors on the cell surface capable of efficient transport of the ligands. In general, incomplete specificity for the target cells and poor internalization of antibody-drug conjugates still limit the usefulness of antibodies for site-specific drug delivery applications necessitating exploration of alternatives. The alternate possibility is to exploit the exquisite cell type specificity and high efficiency of endocytosis of macromolecules mediated by specific receptors present on the surface of target cells for delivering drugs. A large number of infectious, metabolic, and neoplastic diseases are associated with macrophages leading to morbidities and mortalities to millions of people worldwide, thus an appropriate design of a drug delivery system to macrophages will be of tremendous help.

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References

  1. Pearse BMF (1976) Proc Natl Acad Sci USA 73:1255

    Article  CAS  Google Scholar 

  2. Ehrlich P (1906) In: Collected Studies on Immunity, vol 2. John Wiley, New York, pp 442

    Google Scholar 

  3. Fiani ML, Stahl PD (1989) Trends Biotechnol 7:57

    Article  CAS  Google Scholar 

  4. Poznansky MJ, Juliano RL (1984) Pharmacol Rev 36:277

    CAS  Google Scholar 

  5. Basu SK (1990) Biochem Pharmacol 40:1941

    Article  CAS  Google Scholar 

  6. Pastan I, Willingham MC, FitzGerald DJP (1986) Cell 47:641

    Article  CAS  Google Scholar 

  7. Goldstein JL, Basu SK, Brown MS ( 1983) Meth Enzymol 8:241

    Article  Google Scholar 

  8. Basu SK (1984) J Biosci 6:535

    Article  CAS  Google Scholar 

  9. Pearse BMF (1976) Proc Natl Acad Sci USA 73:1255

    Article  CAS  Google Scholar 

  10. Pearse BMF (1988) EMBOJ 7:3331

    CAS  Google Scholar 

  11. Lehrmann MA, Goldstein JL, Brown MS, Russell DW, Schneider WJ (1985) Cell 41:737

    Article  Google Scholar 

  12. Davis CG, Lehrmann MA, Russell DW, Anderson RGW, Brown MS, Goldstein JL (1986) Cell 45:15

    Google Scholar 

  13. Anderson RGW, Brown MS, Goldstein JL (1977) Cell 10:351

    Google Scholar 

  14. Rothenberger S, Iacopetta BJ, Kuhn LC (1987) Cell 49:423

    Google Scholar 

  15. Miettinen.M, Rose JK, Mellman I (1989) Cell 58:317

    Google Scholar 

  16. Kosaka T, Ikeda K (1983) J Cell Biol 97:499

    Google Scholar 

  17. Van der Bliek AM, Meyerowitz EM (1991) Nature 351:411

    Google Scholar 

  18. Scaife R, Margolis RL (1990) J Cell Biol 111:3023

    Google Scholar 

  19. DeLuca-Flaherty C, Mckay DB, Parham P, Hill BL ( 1990) Cell 62:875

    Google Scholar 

  20. Goud B, Zahraoui A, Tavitan A, Saraste J (1990) Nature 345:553

    Google Scholar 

  21. Hopkins CR, Trowbridge IS (1983) J Cell Biol 97:508

    Google Scholar 

  22. Anderson RGW, Falck JR, Goldstein JL, Brown MS ( 1984) Proc Natl Acad Sci USA 81:4838

    Google Scholar 

  23. Stahl P, Schwartz AL (1986) J Clin Invest 77:657

    Google Scholar 

  24. Basu SK, Goldstein JL, Anderson RGW, Brown MS (1981) Cell 24:493

    Google Scholar 

  25. Ezekowitz RAB, Stahl PD (1988) J Cell Sci Suppl 9:121

    Google Scholar 

  26. Hanover CJ, Dickson RB (1985) In: Pastan I, Willingham MC (eds) Endocytosis. Plenum Press, New York, pp 131–162

    Google Scholar 

  27. Unanue ER (1984) Annu Rev Immunol 2:395

    Google Scholar 

  28. Stoschek CM, Carpenter G (1984) J Cell Biol 91:1048

    Google Scholar 

  29. Mostov KE, Friedlander M, Blobel G (1984) Nature 308:37

    Google Scholar 

  30. Blum JS, Diaz R, Mayorga LS, Stahl, PD (1993) Subcellular Biochemistry 9:69

    Google Scholar 

  31. Balch WE (1990) Trends Biochem Sci 15:473

    Google Scholar 

  32. Rothman JE, Sollner TH ( 1997) Science 276:1212

    Google Scholar 

  33. Schimmoller F, Simon I, Pfeffer SR (1998) J Biol Chem 273:22161

    Google Scholar 

  34. Chavrier P, Parton RG, Hauri HP, Simons K, Zerial M (1990) Cell 62:317

    Google Scholar 

  35. Goud B, Zahraoui A, Tavitan A, Saraste J (1990) Nature 345:553

    Google Scholar 

  36. Sluijs V, Hull PM, Zahraoui A, Tavitan A, Goud B, Mellman I ( 1991 ) Proc Natl Acad Sci USA 88:6313

    Google Scholar 

  37. Bucci C, Parton RG, Mather IH, Stunnenberg H, Simons K, Hoflack B, Zerial M (1992) Cell 70:715

    Google Scholar 

  38. Li G, Stahl PD (1993) J Biol Chem 268:24475

    Google Scholar 

  39. Barbieri MA, Li G, Colombo MI, Stahl PD (1994) J Biol Chem 269:18720

    Google Scholar 

  40. Lombardi D, Soldati T, Reiderer MA, Goda Y, Zerial M, Pfeffer SR (1993) EMBO J 12:677

    Google Scholar 

  41. Mukhopadhyay A, Barbieri AM, Funato K, Roberts R, Stahl PD (1997a) J Cell Biol 136:1227

    Google Scholar 

  42. Mukhopadhyay A, Funato F, Stahl PD (1997b) J Biol Chem 272:13055

    Google Scholar 

  43. Diaz R, Mayorga LS, Weidman PJ, Rothman JE, Stahl PD (1989) Nature 339:398

    Google Scholar 

  44. Mayorga LS, Colombo MI, Lennartz M, Brown EJ, Rahman KH, Weiss R, Lennon PJ, Stahl PD (1993) Proc Natl Acad Sci USA 90:20255

    Google Scholar 

  45. Li G, D’Souza-Schorey C, Barbieri MA, Roberts RL, Klippel A, Williams LT, Stahl PD (1995) Proc Natl Acad Sci USA 92:10207

    Google Scholar 

  46. Sollner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE (1993) Nature 362:318

    Google Scholar 

  47. Soggard M, Tani K, Ye R, Geromanos S, Tempst P, Kirchhausen T, Rothman JE, Sollner T (1994) Cell 78:937

    Google Scholar 

  48. Rothman JE, Wieland FT (1996) Science 272:227

    Google Scholar 

  49. Pfeffer SR (1999) Nature Cell Biol 1:E17

    Google Scholar 

  50. Via LE, Deretic D, Ulmer RJ, Hibler NS, Huber LA, Deretic V ( 1997) J Biol Chem 272:13326

    Google Scholar 

  51. Garcia-del Portillo F (1999) Trends Microbiol 6:467

    Google Scholar 

  52. Uchiya K, Barbieri MA, Funato F, Shah AH, Stahl PD, Groisman EA (1999) EMBO J 18:3924

    Google Scholar 

  53. Mukherjee K, Siddiqui S, Hashim S, Raje M, Basu SK, Mukhopadhyay A (2000). J Cell Biol 148:741

    Article  CAS  Google Scholar 

  54. Hashim S, Mukherjee K, Raje M, Basu SK, Mukhopadhyay A (2000) J Biol Chem 275:16281

    Google Scholar 

  55. Gordon S, Rabinowitz S (1989) Adv Drug Deliv Rev 4:27

    Google Scholar 

  56. Fiume L, Busi G, Di Stefano A, Mattioli A ( 1994) Adv Drug Deliv Rev 14:51

    Google Scholar 

  57. Lewis CE, McGee JO (eds) ( 1992) The Macrophage. Oxford University Press, Oxford

    Google Scholar 

  58. Kleinerman ES, Schroit AJ, Fogler WE, Fidler IJ (1983) J Clin Invest 72:1

    Google Scholar 

  59. Mogensen SC (1979) Microbiol Rev 43:1

    Google Scholar 

  60. Schroit AJ, Hart IB, Madsen J, Fidler I (1983) J Biol Resp Modifiers 2:97

    Google Scholar 

  61. Mukherjee K, Parashuraman S, Raje M, Mukhopadhyay A (2001) J Biol Chem 276:23607

    Google Scholar 

  62. Williams AF (1987) Immunol Today 8:298

    Google Scholar 

  63. Rettenmier CW, Roussel MF, Sherr CJ (1988) J Cell Sci Suppl 9:27

    Google Scholar 

  64. Wright SD, Detmers PA (1988) J Cell Sci Suppl 9:99

    Google Scholar 

  65. Mellman I, Koch T, Healey G, Hunzeker W, Lewis V, Plutner H, Miettienen H, Vaux D, Moore K, Stuart S (1988) J Cell Sci Suppl 9:45

    Google Scholar 

  66. Pontow SE, Kery V, Stahl PD (1993) Int Rev Cytol B 137:221

    Google Scholar 

  67. Basu SK, Brown MS, Ho YK, Goldstein JL (1979) J Biol Chem 254:7141

    Google Scholar 

  68. Goldstein JL, Ho YK, Basu SK, Brown MS (1979) Proc Natl Acad Sci USA 76:333

    Google Scholar 

  69. Brown MS, Basu SK, Falck JR, Ho YK, Goldstein JL ( 1980) J Supramol Struct 13:67

    Google Scholar 

  70. Schlesinger PH, Rodman JS, Frey M, Lang S, Stahl PD (1976) Arch Biochem Biophys 177:606

    Google Scholar 

  71. Lee YC, Stowell C, Krantz MJ (1976) Biochemistry 15:3956

    Google Scholar 

  72. Stahl PD (1992) Curr Opinion Immunol 4:49

    Google Scholar 

  73. Ezekowitz RAB, Sastry K, Bailly P, Warner A (1990) J Exp Med 172:1785

    Google Scholar 

  74. Drickamer K (1988) J Biol Chem 263:9557

    Google Scholar 

  75. Stahl PD, Schlesinger PH, Sigardson E, Rodman JS, Lee YC (1980) Cell 19:207

    Google Scholar 

  76. Shepherd VL, Abdolrasulnia R, Garrett M, Cowan HB ( 1990) J Immunol 145:1530

    Google Scholar 

  77. Basu N, Sett R, Das PK (1991) Biochem J 277:451

    Google Scholar 

  78. Goldstein JL, Brown MS, Anderson RGW, Russell DW, Schneider WJ (1985) Annu Rev Cell Biol 1:1

    Google Scholar 

  79. Pearson A, Rich A, Krieger M (1993) J Biol Chem 268:3546

    Google Scholar 

  80. Kodama T, Reddy P, Kishimoto C, Krieger M (1988) Proc Natl Acad Sci USA 85:9238

    Google Scholar 

  81. Krieger M, Herz J ( 1994) Annu Rev Biochem 63:601

    Google Scholar 

  82. Geng Y-J, Hansson GK (1995) Scand J Immunol 42:289

    Google Scholar 

  83. Li H, Freeman MW, Libby P (1995) J Clin Invest 95:122

    Google Scholar 

  84. Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M (1990) Nature 343:531

    Google Scholar 

  85. Rohrer L, Freeman M, Kodama T, Penman M, Krieger M (1990) Nature 343:570

    Google Scholar 

  86. Penman M, Lux A, Freeman M, Rohrer L, Ekkel Y, McKinstry H, Resnick D, Krieger M (1991) J Biol Chem 266:23985

    Google Scholar 

  87. Ashkenas J, Penman M, Vasile E, Acton S, Freeman M, Krieger M (1993) J Lipid Res 34:984

    Google Scholar 

  88. Acton SL, Scherer PE, Lodish HF, Krieger M (1994) J Biol Chem 269:21003

    Google Scholar 

  89. Doi T, Higashino K, Kurihara Y, Wada Y, Miyazaki T, Nakamura H, Uesugi S, Imanishi T, Kawabe Y, Itakura H, Yazaki Y, Matsumoto A, Kodama T (1993) J Biol Chem 268:2126

    Google Scholar 

  90. Mukhopadhyay A, Chaudhuri G, Arora SK, Sehgal S, Basu SK (1989) Science 244:705

    Google Scholar 

  91. Basu S, Mukhopadhyay B, Basu SK, Mukhopadhyay A (1994) FEBS Lett 342:249

    Google Scholar 

  92. Chaudhuri G, Mukhopadhyay A, Basu SK (1989) Biochem Pharmacol 38:2995

    Google Scholar 

  93. Majumdar S, Basu SK (1991) Antimicrob Agents Chemother 335:135

    Google Scholar 

  94. Majumdar S, Basu SK (1995) Drug Delivery 2:144

    Google Scholar 

  95. Prasad V, Hashim S, Mukhopadhyay A, Basu SK, Roy RP (1999) Antimicrob Agents Chemother 43:2689

    Google Scholar 

  96. Unwalla H, Banerjea AC (2001) Biochem J 357:97

    Google Scholar 

  97. Yamashita C, Sone S, Ogura T, Kiwada H (1991) Jpn J Cancer Res 82:569

    Google Scholar 

  98. Muller CD, Schuber F (1989) Biochem Biophys Acta 986:97

    Google Scholar 

  99. Barratt GM, Nolibe D, Yapo A, Petit JF, Tenu JP (1987) Ann Inst Pasteur Immunol 138:437

    Google Scholar 

  100. Surolia A, Bachhawat BK, Poddar SK (1975) Nature 257:802

    Google Scholar 

  101. Garcon N, Gregoriadis G, Taylor M, Summerfield J (1988) Immunology 64:743

    Google Scholar 

  102. Das N, Mahato SB, Naskar K, Ghosh DK, Basu MK (1990) Biochem Med Metabolic Biology 43:133

    Google Scholar 

  103. Basu MK (1994) Biotech Genetic Eng Rev 12:383

    Google Scholar 

  104. Agrawal AK, Gupta CM (2000) Adv Drug Del Rev 41:135

    Google Scholar 

  105. Chakraborty P, Bhaduri AN, Das PK (1990) Biochem Biophys Res Commun 166:404

    Google Scholar 

  106. Mukhopadhyay A, Mukhopadhyay B, Srivastava RK, Basu SK (1992) Biochem J 284:237

    Google Scholar 

  107. Mukhopadhyay B, Mukhopadhyay A, Basu SK (1993) Biochem Pharmacol 46:919

    Google Scholar 

  108. Dumont S, Muller CD, Schuber F, Bartholeyns J (1990) Anticancer Res 10:155–160

    Google Scholar 

  109. Simmons BM, Stahl PD, Russell JH (1986) J Biol Chem 261:7912

    Google Scholar 

  110. Skilleter DN, Foxwell BMJ (1986) FEBS Lett 196:344

    Google Scholar 

  111. Mukhopadhyay A, Mukhopadhyay B, Basu SK (1995) FEBS Lett 376:95

    Google Scholar 

  112. Srividya S, Roy RP, Basu SK, Mukhopadhyay A (2000) J Leucocyte Biol 67:683

    Google Scholar 

  113. Srividya S, Roy RP, Basu SK, Mukhopadhyay A (2000) Biochem Biophys Res Commun 268:772

    Google Scholar 

  114. Abraham R, Singh N, Mukhopadhyay A, Basu SK, Bal V, Rath S ( 1995) J Immunol 154:1

    Google Scholar 

  115. Abraham R, Choudhury A, Basu SK, Bal V, Rath S (1997) J Immunol 158:4029

    Google Scholar 

  116. Singh N, Bhatia S, Abraham R, Basu SK, George A, Bal V, Rath S (1998) J Immunol 160:4869

    Google Scholar 

  117. Bansal P, Mukherjee P, Basu SK, George A, Bal V, Rath S (1999) J Immunol 162:4430

    Google Scholar 

  118. Bhatia S, Mukhopadhyay S, Jarman E, Hall G, George A, Basu SK, Rath S, Lamb JR, Bal V (2002) J Allergy Clin Immunol 109:321

    Google Scholar 

  119. Choudhury A, Mukherjee P, Basu SK, George A, Bal V, Rath S (2000) J Immunol 164:1713

    Google Scholar 

  120. Levitzki A (1996) Curr Opin Cell Biol 8:240

    Google Scholar 

  121. Fry DW, Kraker AJ, McMichael A, Ambroso A, Nelson JM, Leopold WR, Connors RW, Bridges AJ (1994) Science 9:1093

    Google Scholar 

  122. Mayden N, Gruenberger T, Dadi H, Shahar M, Arpaia E, Lapidot Z, Leader S, Freedman M, Cohan A, Gazit A (1996) Nature 379:645

    Google Scholar 

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Mukhopadhyay, A., Basu, S.K. (2003). Intracellular Delivery of Drugs to Macrophages. In: Ghose, T.K., et al. Biotechnology in India I. Advances in Biochemical Engineering/Biotechnology, vol 84. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-36488-9_6

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