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Toward a new generation of therapeutics

Artificial cell targeted delivery of live cells for therapy

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Abstract

Scientific evidence in the prevention and treatment of various disorders is accumulating regarding probiotics. The health benefits supported by adequate clinical data include increased resistance to infectious disease, decreased duration of diarrhea, management of inflammatory bowel disease, reduction of serum cholesterol, prevention of allergy, modulation of cytokine gene expression, and suppression of carcinogen production. Recent ventures in metabolic engineering and heterologous protein expression have enhanced the enzymatic and immunomodulatory effects of probiotics and, with time, may allow more active intervention among critical care patients. In addition, a number of approaches are currently being explored, including the physical and chemical protection of cells, to increase probiotic viability and its health benefits. Traditional immobilization of probiotics in gel matrices, most notably calcium alginate and κ-carrageenan, has frequently been employed, with noted improvements in viability during freezing and storage. Conflicting reports exist, however, on the protection offered by immobilization from harsh physiologic environments. An alternative approach, microencapsulation in “artificial cells,” builds on immobilization technologies by combining enhanced mechanical stability of the capsule membrane with improved mass transport, increased cell loading, and greater control of parameters. This review summarizes the current clinical status of probiotics, examines the promises and challenges of current immobilization technologies, and presents the concept of artificial cells for effective delivery of therapeutic bacterial cells.

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References

  1. Roberfroid, M. B. (2000), Am. J. Clin. Nutr. 71, 1682S-1687S.

    CAS  Google Scholar 

  2. Metchnikoff, E. (1908), The Prolongation of Life, G. P. Putnam’s Sons, New York.

    Google Scholar 

  3. Shah, N P. (2000), J. Dairy Sci. 83, 894–907.

    CAS  Google Scholar 

  4. Audet, P., Paquin, C., and Lacroix, C. (1988), Appl. Microbiol. Biotechnol. 29, 11–18.

    CAS  Google Scholar 

  5. Chandramouli, V., Kailasapathy, K., Peiris, P., and Jones, M. (2004), J. Microbiol. Methods 56, 27–35.

    CAS  Google Scholar 

  6. Hansen, L. T., Allan-Wojtas, P. M., Jin, Y. L., and Paulson, A. T. (2002), Food Microbiol. 19, 35–45.

    CAS  Google Scholar 

  7. Park, J. K. and Chang, H. N. (2000), Biotechnol. Adv. 18, 303–319.

    CAS  Google Scholar 

  8. Chang, T. M. S. (1964), Science 146, 524–525.

    CAS  Google Scholar 

  9. Gill, H. S. and Guarner, F. (2004), Postgrad. Med. J. 80, 516–526.

    CAS  Google Scholar 

  10. Gionchetti, P., Rizzello, F., Venturi, A., and Campieri, M. (2000), J. Gastroenterol. Hepatol. 15, 489–493.

    CAS  Google Scholar 

  11. Huang, J. S., Bousvaros, A., Lee, J. W., Diaz, A., and Davidson, E. J. (2002), Dig. Dis. Sci. 47, 2625–2634.

    CAS  Google Scholar 

  12. Szajewska, H. and Mrukowicz, J. Z. (2001), J. Pediatr. Gastroenterol. Nutr. 33(Suppl. 2), S17-S25.

    CAS  Google Scholar 

  13. Szajewska, H., Kotowska, M., Mrukowicz, J. Z., Armanska, M., and Mikolajczyk, W. (2001), J. Pediatr. 138, 361–365.

    CAS  Google Scholar 

  14. Aso, Y., Akaza, H., Kotake, T., Tsukamoto, T., Imai, K., and Naito, S. (1995), Eur. Urol. 27, 104–109.

    CAS  Google Scholar 

  15. McIntosh, G. H., Royle, P. J., and Playne, M. J. (1999), Nutr. Cancer 35, 153–159.

    CAS  Google Scholar 

  16. Singh, J., Rivenson, A., Tomita, M., Shimamura, S., Ishibashi, N., and Reddy, B. S. (1997), Carcinogenesis 18, 833–841.

    CAS  Google Scholar 

  17. Rayes, N., Seehofer, D., Hansen, S., et al. (2002), Transplantation 74, 123–127.

    Google Scholar 

  18. Lodinova-Zadnikova, R. and Sonnenborn, U. (1997), Biol. Neonate 71, 224–232.

    CAS  Google Scholar 

  19. Bukowska, H., PieczulMroz, J., Chelstowski, K., and Naruszewicz, M. (1997), Atherosclerosis 134, 325.

    Google Scholar 

  20. Steidler, L., Hans, W., Schotte, L., et al. (2000), Science 289, 1352–1355.

    CAS  Google Scholar 

  21. Steidler, L. (2002), Antonie Van Leeuwenhoek 82, 323–331.

    CAS  Google Scholar 

  22. Gill, H. S. (1998), Int. Dairy. J. 8, 535–544.

    CAS  Google Scholar 

  23. Meydani, S. N. and Ha, W. K. (2000), Am. J. Clin. Nutr. 71, 861–872.

    CAS  Google Scholar 

  24. Gill, H. S. (2003), Best Pract. Res. Clin. Gastroenterol. 17, 755–773.

    CAS  Google Scholar 

  25. Guarner, F. and Malagelada, J. R. (2003), Best Pract. Res. Clin. Gastroenterol. 17, 793–804.

    CAS  Google Scholar 

  26. Van’t Veer, P., Dekker, J., Lamers, J., et al. (1989), Cancer Res. 49, 4020–4023.

    Google Scholar 

  27. Kirjavainen, P. V., Salminen, S. J., and Isolauri, E. (2003), J. Pediatr. Gastroenterol. Nutr. 36, 223–227.

    Google Scholar 

  28. Matricardi, P. M., Bjorksten, B., Bonini, S., et al. (2003), Allergy 58, 461–471.

    CAS  Google Scholar 

  29. Gilliland, S. E., Nelson, C. R., and Maxwell, C. (1985), Appl. Environ. Microbiol. 49, 377–381.

    CAS  Google Scholar 

  30. Schaafsma, G., Meuling, W. J., van Dokkum, W., and Bouley, C. (1998), Eur. J. Clin. Nutr. 52, 436–440.

    CAS  Google Scholar 

  31. Godward, G. and Kailasapathy, K. (2003), Milchwissenschaft-Milk Sci. Int. 58, 396–399.

    Google Scholar 

  32. Wang, Y. C., Yu, R. C., and Chou, C. C. (2004), Int. J. Food Microbiol. 93, 209–217.

    Google Scholar 

  33. Holzapfel, W. H., Haberer, P., Snel, J., Schillinger, U., and Huis in’t Veld, J. H. J. (1998), Int. J. Food Microbiol. 41, 85–101.

    CAS  Google Scholar 

  34. Huang, Y. and Adams, M. C. (2004), Int. J. Food Microbiol. 91, 253–260.

    Google Scholar 

  35. Salminen, S., von Wright, A., Morelli, L., et al. (1998), Int. J. Food Microbiol. 44, 93–106.

    CAS  Google Scholar 

  36. Lu, L. and Walker, W. A. (2001), Am. J. Clin. Nutr. 73, 1124S-1130S.

    CAS  Google Scholar 

  37. Saavedra, J. M. and Tschernia, A. (2002), Br. J. Nutr. 87, S241-S246.

    Article  CAS  Google Scholar 

  38. Vitini, E., Alvarez, S., Medina, M., Medici, M., de Budeguer, M. V., and Perdigon, G. (2000), Biocell 24, 223–232.

    CAS  Google Scholar 

  39. Chin, J., Turner, B., Barchia, I., and Mullbacher, A. (2000), Immunol. Cell Biol. 78, 55–66.

    CAS  Google Scholar 

  40. Karel, S. F., Libicki, S. B., and Robertson, C. R. (1985), Chem. Eng. Sci. 40, 1321–1354.

    CAS  Google Scholar 

  41. Witter, L. (1996), in Physical Chemistry of Food Processes, van Nostrand Reinhold, New York, pp. 475–486.

    Google Scholar 

  42. Babu, P. S., Panda, T., and Babu, M. K. M. (1991), Enzyme Microb. Technol. 13, 676–682.

    CAS  Google Scholar 

  43. Adhikari, K., Mustapha, A., Grun, I. U., and Fernando, L. (2000), J. Dairy Sci. 83, 1946–1951.

    Article  CAS  Google Scholar 

  44. Sheu, T. Y. and Marshall, R. T. (1993), J. Food Sci. 58, 557–561.

    Google Scholar 

  45. Kebary, K. M. K., Hussein, S. A., and Badawi, R. M. (1998), Egypt. J. Dairy Sci. 26, 319–337.

    Google Scholar 

  46. Sultana, K., Godward, G., Reynolds, N., Arumugaswamy, R., Peiris, P., and Kailasapathy, K. (2000), Int. J. Food Microbiol. 62, 47–55.

    CAS  Google Scholar 

  47. Kim, Y. D., Morr, C. V., and Schenz, T. W. (1996), J. Agric. Food Chem. 44, 1308–1313.

    CAS  Google Scholar 

  48. Shah, N. P. and Ravula, R. R. (2000), Aust. J. Dairy Technol. 55, 139–144.

    Google Scholar 

  49. Lee, K. Y. and Heo, T. R. (2000), Appl. Environ. Microbiol. 66, 869–873.

    CAS  Google Scholar 

  50. Audet, P., Paquin, C., and Lacroix, C. (1990), Appl. Microbiol. Biotechnol. 32, 662–668.

    CAS  Google Scholar 

  51. Audet, P., Paquin, C., and Lacroix, C. (1991), Biotechnol. Techniques 5, 307–312.

    Google Scholar 

  52. Sun, W. and Griffiths, M. W. (2000), Int. J. Food Microbiol. 61, 17–25.

    CAS  Google Scholar 

  53. Narayani, R. and Rao, K. P. (1993), Int. J. Pharmaceutics 95, 85–91.

    CAS  Google Scholar 

  54. Narayani, R. and Rao, K. P. (1995), J. Biomater. Sci.-Polym. Ed. 7, 39–48.

    CAS  Google Scholar 

  55. Crittenden, R., Laitila, A., Forssell P., et al. (2001), Appl. Environ. Microbiol. 67, 3469–3475.

    CAS  Google Scholar 

  56. Wang, X., Brown, I. L., Evans, A. J., and Conway, P. L. (1999), J. Appl. Microbiol. 87, 631–639.

    CAS  Google Scholar 

  57. Prevost, H. and Divies, C. (1992), Biotechnol. Lett. 14, 583–588.

    CAS  Google Scholar 

  58. Favoro-Trindade, C. S. and Grosso, C. R. (2002), J. Microencapsul., 19, 485–494.

    Google Scholar 

  59. Rao, A. V., Shiwrarain, N., and Maharaj, I. (1989), Can. Inst. Food Sci. Technol. J. 22, 345–349.

    Google Scholar 

  60. Sanderson, G. R. (1990), in Food Gels, Elsevier, New York, pp. 201–233.

    Google Scholar 

  61. Esquisabel, A., Hernandez, R. M., Igartua, M., Gascon, A. R., Calvo, B., and Pedraz, J. L. (2002), J. Microencapsul. 19, 237–244.

    CAS  Google Scholar 

  62. Losgen, H., Brunner, G., Holloway, C. J., et al. (1978), Biomater. Med. Devices Artif. Organs 6, 151–173.

    CAS  Google Scholar 

  63. Hou, R. C., Lin, M. Y., Wang, M. M., and Tzen, J. T. (2003), J. Dairy Sci. 86, 424–428.

    Article  CAS  Google Scholar 

  64. O’Riordan, K., Andrews, D., Buckle, K., and Conway, P. (2001), J. Appl. Microbiol. 91, 1059–1066.

    CAS  Google Scholar 

  65. Chang, T. M. S., MacIntosh, F. C., and Mason, S. G. (1966), Can. J. Physiol. Pharmacol. 44, 115–128.

    CAS  Google Scholar 

  66. Chang, T. M. S. and Prakash, S. (1998), Mol. Med. Today 4, 221–227.

    CAS  Google Scholar 

  67. Lim, F. and Sun, A. M. (1980), Science 210, 908–910.

    CAS  Google Scholar 

  68. Prakash, S. and Chang, T. M. S. (1996), Nat. Med. 2, 883–887.

    CAS  Google Scholar 

  69. Prakash, S. and Chang, T. M. S. (1999), Artif. Cells Blood Substitutes Immobilization Biotechnol. 27, 475–481.

    CAS  Google Scholar 

  70. Prakash, S. and Chang, T. M. S. (2000), Int. J. Artif. Organs 23, 429–435.

    CAS  Google Scholar 

  71. Uludag, H., de Vos, P., and Tresco, P. A. (2000), Adv. Drug Deliv. Rev. 42, 29–64.

    CAS  Google Scholar 

  72. Strand, B. L., Ryan, L., Veld, P. I., et al., (2001), Cell Transplant. 10, 263–275.

    CAS  Google Scholar 

  73. Gugerli, R., Cantana, E., Heinzen, C., von Stockar, U., and Marison, I. W. (2002), J. Microencapsul. 19, 571–590.

    CAS  Google Scholar 

  74. Ma, X. J., Vacek, I., and Sun, A. (1994), Artif. Cells Blood Substitutes Immobilization Biotechnol. 22, 43–69.

    CAS  Google Scholar 

  75. Quong, D., Yeo, J. N., and Neufeld, R. J. (1999), J. Microencapsul. 16, 73–82.

    CAS  Google Scholar 

  76. Petruzzo, P., Cappai, A., Ruiu, G., Dessy, E., Rescigno, A., and Brotzu, G. (1997), Transplant. Proc. 29, 2129–2130.

    CAS  Google Scholar 

  77. Bartkowiak, A. and Hunkeler, D. (1999), Bioartif. Organs Technol., Med., Mater. 875, 219–232.

    Google Scholar 

  78. Calafiore, R., Basta, G., Luca, G., et al. (1999), Ann. NY Acad Sci. 875, 219–232.

    CAS  Google Scholar 

  79. Wang, T., Lacik, I., Brissova, M., et al. (1997), Nat. Biotechnol. 15, 358–362.

    CAS  Google Scholar 

  80. Ouyang, W., Chen, H., Jones, M. L., et al. (2004), J. Pharm. Pharmaceut. Sci. 7, 315–324.

    CAS  Google Scholar 

  81. Tse, M., Uludag, H., Sefton, M. V., and Chang, P. L. (1996), Biotechnol. Bioeng. 51, 271–280.

    CAS  Google Scholar 

  82. Awrey, D. E., Tse, M., Hortelano, G., and Chang, P. L. (1996), Biotechnol. Bioeng. 52, 472–484.

    CAS  Google Scholar 

  83. Strand, B. L., Gaserod, O., Kulseng, B., Espevik, T., and Skjak-Baek, G. (2002), J. Microencapsul 19, 615–630.

    CAS  Google Scholar 

  84. Bartkowiak, A. and Hunkeler, D. (2000), Chem. Mater. 12, 206–212.

    CAS  Google Scholar 

  85. Bartkowiak, A. (2001), Ann. NY Acad. Sci. 944, 120–134.

    Article  CAS  Google Scholar 

  86. Haque, T., Chen, H., Ouyang, W., et al. (2005), Mol. Pharm. 2, 29–36.

    CAS  Google Scholar 

  87. Lacik, I., Brissova, M., Anilkumar, A. V., Powers, A. C., and Wang, T. (1998), J. Biomed. Mater. Res. 39, 52–60.

    CAS  Google Scholar 

  88. Rehor, A., Canaple, L., Zhang, Z., and Hunkeler, D. (2001), J. Biomater. Sci. Polym. Ed. 12, 157–170.

    CAS  Google Scholar 

  89. Crooks, C. A., Douglas, J. A., Broughton, R. L., and Sefton, M. V. (1990), J. Biomed. Mater. Res. 24, 1241–1262.

    CAS  Google Scholar 

  90. Wong, H. and Chang, T. M. S. (1991), Biomater. Artif. Cells Immobilization Biotechnol. 19, 687–697.

    CAS  Google Scholar 

  91. Siuta-Cruce, P. and Goulet, J. (2001), Food Technol. 55, 36–42.

    CAS  Google Scholar 

  92. Institut Rosell-Lallemand (2002), Newsletter Number 2, Institut Rosell-Lallemand, Montreal, QC, Canada.

    Google Scholar 

  93. Steidler, L. (2003), Best Pract. Res. Clin. Gastroenterol. 17, 861–876.

    Google Scholar 

  94. Federici, F., Vitali, B., Gotti, R., et al. (2004), Appl. Environ. Microbiol. 70, 5066–5073.

    CAS  Google Scholar 

  95. Rodby, R. A., Tyszka, T. S., and Williams, J. W. (1991), Am. J. Med. 90, 498–504.

    CAS  Google Scholar 

  96. Williams, H. E. and Smith, L. H., Jr. (1968), Am. J. Med. 45, 715–735.

    CAS  Google Scholar 

  97. Goldkin, L., Cave, D., Jaffin, B., Robinson, W., and Bliss, C. (1985), Am. J. Gastroenterol 80, 860–865.

    Google Scholar 

  98. Chow, K. M., Liu, Z. C., Prakash, S., and Chang, T. M. S. (2003), Artif. Cells Blood Substitutes Immobilization Biotechnol. 31, 425–434.

    CAS  Google Scholar 

  99. Prakash, S. and Chang, T. M. S. (1995), Biotechnol. Bioeng. 46, 621–626.

    CAS  Google Scholar 

  100. Duncan, S. H., Richardson, A. J., Kaul, P., Holmes, R. P., Allison, M. J., and Stewart, C. S. (2002), Appl. Environ. Microbiol. 68, 3841–3847.

    CAS  Google Scholar 

  101. De Smet, I., Vanhoorde, L., Desaeyer, N., Vandewoestyne, M., and Verstraete, W. (1994), Microbiol. Ecol. Health Dis. 7, 315–329.

    Article  Google Scholar 

  102. Jones, M., Chen, H., Ouyang, W., Metz, T., and Prakash, S. (2004), J. Biomed. Biotechnol. 1, 61–69.

    Google Scholar 

  103. De Boever, P., Wouters, R., Verschaeve, L., Berckmans, P., Schoeters, G., and Verstraete, W. (2000), Appl. Microbiol. Biotechnol. 53, 709–714.

    Google Scholar 

  104. De Smet, I., Vanhoorde, L., Woestyne, M. V., Christiaens, H., and Verstraete, W. (1995), J. Appl. Bacteriol. 79, 292–301.

    Google Scholar 

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Prakash, S., Martoni, C. Toward a new generation of therapeutics. Appl Biochem Biotechnol 128, 1–21 (2006). https://doi.org/10.1385/ABAB:128:1:001

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