Organ Preservation, Ischemia Reperfusion Injury, and Nanotherapeutics in Transplantation

  • Kunal J. Patel
  • Carl Atkinson
  • Ann-Marie Broome
  • Satish N. NadigEmail author


Over the past 30 years, solid organ transplantation has advanced tremendously in many facets, with great strides made in organ selection and allocation to the monitoring and treatment of rejection. Despite these breakthroughs, organ preservation and chronic rejection rates have remained largely unchanged. Recent trends in translational research have begun to address this issue, and future directions for organ preservation will have far-reaching implications for the field of transplantation as a whole. In this chapter, we will highlight the current trends and innovations in preservation techniques, with a special focus on the role that nanotechnology is playing in this frontier.


  1. 1.
    Guibert, E. E., et al. (2011). Organ preservation: Current concepts and new strategies for the next decade. Transfusion Medicine and Hemotherapy : Offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie, 38, 125–142. doi: 10.1159/000327033.CrossRefGoogle Scholar
  2. 2.
    Collins, G. M., Hartley, L. C., & Clunie, G. J. (1972). Kidney preservation for transportation. Experimental analysis of optimal perfusate composition. The British Journal of Surgery, 59, 187–189.CrossRefPubMedGoogle Scholar
  3. 3.
    Andrews, P. M., & Bates, S. B. (1985). Improving Euro-Collins flushing solution’s ability to protect kidneys from normothermic ischemia. Mineral and Electrolyte Metabolism, 11, 309–313.PubMedGoogle Scholar
  4. 4.
    Kalayoglu, M., et al. (1988). Extended preservation of the liver for clinical transplantation. Lancet (London, England), 1, 617–619.Google Scholar
  5. 5.
    Fukuse, T., et al. (1996). Comparison of low potassium Euro-Collins solution and standard Euro-Collins solution in an extracorporeal rat heart-lung model. European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, 10, 621–627.CrossRefGoogle Scholar
  6. 6.
    Adam, R., et al. (2015). Compared efficacy of preservation solutions in liver transplantation: A long-term graft outcome study from the European Liver Transplant Registry. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 15, 395–406. doi: 10.1111/ajt.13060.CrossRefGoogle Scholar
  7. 7.
    Garcia-Gil, F. A., et al. (2014). Evaluation of Institut Georges Lopez-1 preservation solution in pig pancreas transplantation: A pilot study. Transplantation, 97, 901–907. doi: 10.1097/tp.0000000000000050.CrossRefPubMedGoogle Scholar
  8. 8.
    Aziz, T. M., et al. (2003). Perfadex for clinical lung procurement: Is it an advance? The Annals of Thoracic Surgery, 75, 990–995.CrossRefPubMedGoogle Scholar
  9. 9.
    Belzer, F. O., & Southard, J. H. (1988). Principles of solid-organ preservation by cold storage. Transplantation, 45, 673–676.CrossRefPubMedGoogle Scholar
  10. 10.
    Drinkwater, D. C., Jr., et al. (1995). Extracellular and standard University of Wisconsin solutions provide equivalent preservation of myocardial function. The Journal of Thoracic and Cardiovascular Surgery, 110, 738–745. doi: 10.1016/s0022-5223(95)70106-0.CrossRefPubMedGoogle Scholar
  11. 11.
    Roskott, A. M., et al. (2011). Small bowel preservation for intestinal transplantation: A review. Transplant International : Official Journal of the European Society for Organ Transplantation, 24, 107–131. doi: 10.1111/j.1432-2277.2010.01187.x.CrossRefGoogle Scholar
  12. 12.
    Latchana, N., et al. (2015). Preservation solutions used during abdominal transplantation: Current status and outcomes. World Journal of Transplantation, 5, 154–164. doi: 10.5500/wjt.v5.i4.154.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Binns, O. A., et al. (1996). Both blood and crystalloid-based extracellular solutions are superior to intracellular solutions for lung preservation. The Journal of Thoracic and Cardiovascular Surgery, 112, 1515–1521. doi: 10.1016/s0022-5223(96)70010-7.CrossRefPubMedGoogle Scholar
  14. 14.
    Keshavjee, S. H., et al. (1992). The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation. The Journal of Thoracic and Cardiovascular Surgery, 103, 314–325.PubMedGoogle Scholar
  15. 15.
    Oto, T., et al. (2006). Early outcomes comparing Perfadex, Euro-Collins, and Papworth solutions in lung transplantation. The Annals of Thoracic Surgery, 82, 1842–1848. doi: 10.1016/j.athoracsur.2006.05.088.CrossRefPubMedGoogle Scholar
  16. 16.
    Marasco, S. F., et al. (2011). Effect of donor preservation solution and survival in lung transplantation. The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, 30, 414–419. doi: 10.1016/j.healun.2010.10.002.CrossRefGoogle Scholar
  17. 17.
    Divisi, D., et al. (2001). A comparative study of Euro-Collins, low potassium University of Wisconsin and cold modified blood solutions in lung preservation in acute autotransplantations in the pig. European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, 19, 333–338.CrossRefGoogle Scholar
  18. 18.
    Nath, D. S., et al. (2005). Does Perfadex affect outcomes in clinical lung transplantation? The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, 24, 2243–2248. doi: 10.1016/j.healun.2005.06.019.CrossRefGoogle Scholar
  19. 19.
    Baicu, S. C., Taylor, M. J., & Brockbank, K. G. (2006). The role of preservation solution on acid-base regulation during machine perfusion of kidneys. Clinical Transplantation, 20, 113–121. doi: 10.1111/j.1399-0012.2005.00451.x.CrossRefPubMedGoogle Scholar
  20. 20.
    Baicu, S. C., & Taylor, M. J. (2002). Acid-base buffering in organ preservation solutions as a function of temperature: New parameters for comparing buffer capacity and efficiency. Cryobiology, 45, 33–48.CrossRefPubMedGoogle Scholar
  21. 21.
    Peltz, M., Milchgrub, S., Jessen, M. E., & Meyer, D. M. (2010). Effect of pyruvate and HEPES on rat lung allograft acidosis and cell death after long-term hypothermic storage. Transplantation Proceedings, 42, 2771–2776. doi: 10.1016/j.transproceed.2010.06.004.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sumimoto, R., et al. (1992). A comparison of histidine lactobionate solution with University of Wisconsin solution for rat liver and heart preservation. Transplant International : Official Journal of the European Society for Organ Transplantation, 5(Suppl 1), S408–S410.CrossRefGoogle Scholar
  23. 23.
    Becker, T., et al. (2007). Pancreas transplantation with histidine-tryptophan-ketoglutarate (HTK) solution and University of Wisconsin (UW) solution: Is there a difference? JOP : Journal of the Pancreas, 8, 304–311.PubMedGoogle Scholar
  24. 24.
    Feng, L., et al. (2007). Histidine-tryptophan-ketoglutarate solution vs. University of Wisconsin solution for liver transplantation: A systematic review. Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 13, 1125–1136. doi: 10.1002/lt.21208.CrossRefGoogle Scholar
  25. 25.
    O'Callaghan, J. M., Knight, S. R., Morgan, R. D., & Morris, P. J. (2012). Preservation solutions for static cold storage of kidney allografts: A systematic review and meta-analysis. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 12, 896–906. doi: 10.1111/j.1600-6143.2011.03908.x.CrossRefGoogle Scholar
  26. 26.
    Li, Y., et al. (2015). Three preservation solutions for cold storage of heart allografts: A systematic review and meta-analysis. Artificial Organs. doi: 10.1111/aor.12585.CrossRefPubMedGoogle Scholar
  27. 27.
    Gohrbandt, B., et al. (2015). Lung preservation with perfadex or celsior in clinical transplantation: A retrospective single-center analysis of outcomes. Transplantation, 99, 1933–1939. doi: 10.1097/tp.0000000000000578.CrossRefPubMedGoogle Scholar
  28. 28.
    Petit, P. X., et al. (1998). Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: The impact of irreversible permeability transition. FEBS Letters, 426, 111–116.CrossRefPubMedGoogle Scholar
  29. 29.
    Parrish, D., et al. (2015). New low-volume resuscitation solutions containing PEG-20k. The Journal of Trauma and Acute Care Surgery, 79, 22–29. doi: 10.1097/ta.0000000000000682.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Parrish, D., Lindell, S. L., Reichstetter, H., Aboutanos, M., & Mangino, M. J. (2016). Cell Impermeant-based low-volume resuscitation in hemorrhagic shock: A biological basis for injury involving cell swelling. Annals of Surgery, 263, 565–572. doi: 10.1097/sla.0000000000001049.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Sundberg, R., Ar'rajab, A., Ahren, B., & Bengmark, S. (1991). The functional effects of suppression of hypothermia-induced cell swelling in liver preservation by cold storage. Cryobiology, 28, 150–158.CrossRefPubMedGoogle Scholar
  32. 32.
    Muhlbacher, F., Langer, F., & Mittermayer, C. (1999). Preservation solutions for transplantation. Transplantation Proceedings, 31, 2069–2070.CrossRefPubMedGoogle Scholar
  33. 33.
    Jamart, J., & Lambotte, L. (1983). Efficiency and limitation of Euro-Collins solution in kidney preservation. The Journal of Surgical Research, 34, 195–204.CrossRefPubMedGoogle Scholar
  34. 34.
    Fukuda, C., Kollmar, O., Schafer, T., Tian, Y. H., & Schilling, M. K. (2002). Anionic polysaccharides. A class of substances with hepatoprotective and antiadhesive properties in rat liver preservation. Transplant International : Official Journal of the European Society for Organ Transplantation, 15, 17–23. doi: 10.1007/s00147-001-0374-9.CrossRefGoogle Scholar
  35. 35.
    Ahmed, I., Attia, M. S., Corps, C. L., Lodge, J. P., & Potts, D. J. (2001). Protective effects of lactobionate in modified phosphate-buffered sucrose. Transplantation Proceedings, 33, 950–951.CrossRefPubMedGoogle Scholar
  36. 36.
    Mees, N., Southard, J. H., & Belzer, F. O. (1982). Inhibition of ischemic induced cellular swelling in kidney cortex tissue by lactobionate anions. The Journal of Trauma, 22, 118–120.CrossRefPubMedGoogle Scholar
  37. 37.
    Upadhya, G. A., & Strasberg, S. M. (2000). Glutathione, lactobionate, and histidine: Cryptic inhibitors of matrix metalloproteinases contained in University of Wisconsin and histidine/tryptophan/ketoglutarate liver preservation solutions. Hepatology (Baltimore, MD), 31, 1115–1122. doi: 10.1053/he.2000.6780.CrossRefGoogle Scholar
  38. 38.
    Ar'Rajab, A., Ahren, B., Sundberg, R., & Bengmark, S. (1991). The function of a colloid in liver cold-storage preservation. Transplantation, 52, 34–38.CrossRefPubMedGoogle Scholar
  39. 39.
    Howden, B. O., et al. (1990). Liver preservation with UW solution. I. Evidence that hydroxyethyl starch is not essential. Transplantation, 49, 869–872.CrossRefPubMedGoogle Scholar
  40. 40.
    Biguzas, M., et al. (1990). Evaluation of UW solution in a rat kidney preservation model. I. Effect of hydroxyethyl starch and electrolyte composition. Transplantation, 49, 872–875.CrossRefPubMedGoogle Scholar
  41. 41.
    Mutter, T. C., Ruth, C. A., & Dart, A. B. (2013). Hydroxyethyl starch (HES) versus other fluid therapies: Effects on kidney function. The Cochrane Database of Systematic Reviews, 7, CD007594. doi: 10.1002/14651858.CD007594.pub3.CrossRefGoogle Scholar
  42. 42.
    Morariu, A. M., et al. (2003). Hyperaggregating effect of hydroxyethyl starch components and University of Wisconsin solution on human red blood cells: A risk of impaired graft perfusion in organ procurement? Transplantation, 76, 37–43. doi: 10.1097/ Scholar
  43. 43.
    Mosbah, I. B., et al. (2006). Effects of polyethylene glycol and hydroxyethyl starch in University of Wisconsin preservation solution on human red blood cell aggregation and viscosity. Transplantation Proceedings, 38, 1229–1235. doi: 10.1016/j.transproceed.2006.02.068.CrossRefPubMedGoogle Scholar
  44. 44.
    Bakaltcheva, I., Ganong, J. P., Holtz, B. L., Peat, R. A., & Reid, T. (2000). Effects of high-molecular-weight cryoprotectants on platelets and the coagulation system. Cryobiology, 40, 283–293. doi: 10.1006/cryo.2000.2247.CrossRefPubMedGoogle Scholar
  45. 45.
    Bejaoui, M., et al. (2015). Protective effect of intravenous high molecular weight polyethylene glycol on fatty liver preservation. BioMed Research International, 2015, 794287. doi: 10.1155/2015/794287.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Bejaoui, M., et al. (2016). Polyethylene glycol preconditioning: An effective strategy to prevent liver ischemia reperfusion injury. Oxidative Medicine and Cellular Longevity, 2016, 9096549. doi: 10.1155/2016/9096549.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Xu, X., et al. (2015). High-molecular-weight polyethylene glycol inhibits myocardial ischemia-reperfusion injury in vivo. The Journal of Thoracic and Cardiovascular Surgery, 149, 588–593. doi: 10.1016/j.jtcvs.2014.10.074.CrossRefPubMedGoogle Scholar
  48. 48.
    Malhotra, R., et al. (2011). High-molecular-weight polyethylene glycol protects cardiac myocytes from hypoxia- and reoxygenation-induced cell death and preserves ventricular function. American Journal of Physiology. Heart and Circulatory Physiology, 300, H1733–H1742. doi: 10.1152/ajpheart.01054.2010.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Hauet, T., et al. (2002). Polyethylene glycol reduces the inflammatory injury due to cold ischemia/reperfusion in autotransplanted pig kidneys. Kidney International, 62, 654–667. doi: 10.1046/j.1523-1755.2002.00473.x.CrossRefPubMedGoogle Scholar
  50. 50.
    Faure, J. P., et al. (2004). Protective roles of polyethylene glycol and trimetazidine against cold ischemia and reperfusion injuries of pig kidney graft. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 4, 495–504. doi: 10.1111/j.1600-6143.2004.00365.x.CrossRefGoogle Scholar
  51. 51.
    Murad, K. L., Gosselin, E. J., Eaton, J. W., & Scott, M. D. (1999). Stealth cells: Prevention of major histocompatibility complex class II-mediated T-cell activation by cell surface modification. Blood, 94, 2135–2141.PubMedGoogle Scholar
  52. 52.
    Dondero, F., et al. (2010). A randomized study comparing IGL-1 to the University of Wisconsin preservation solution in liver transplantation. Annals of Transplantation, 15, 7–14.PubMedGoogle Scholar
  53. 53.
    Codas, R., et al. (2009). IGL-1 solution in kidney transplantation: First multi-center study. Clinical Transplantation, 23, 337–342. doi: 10.1111/j.1399-0012.2009.00959.x.CrossRefPubMedGoogle Scholar
  54. 54.
    Yu, W. M., Coddington, D., & Bitter-Suermann, H. (1990). Rat liver preservation. I. The components of UW solution that are essential to its success. Transplantation, 49, 1060–1066.CrossRefPubMedGoogle Scholar
  55. 55.
    Petsikas, D., et al. (1990). Enhanced 24-hour in vitro heart preservation with adenosine and adenosine monophosphate. The Journal of Heart Transplantation, 9, 114–118.PubMedGoogle Scholar
  56. 56.
    Corps, C. L., et al. (2009). Influence on energy kinetics and histology of different preservation solutions seen during cold ischemia in the liver. Transplantation Proceedings, 41, 4088–4093. doi: 10.1016/j.transproceed.2009.07.107.CrossRefPubMedGoogle Scholar
  57. 57.
    Janssen, H., Janssen, P. H., & Broelsch, C. E. (2004). UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury. Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10, 1514–1523. doi: 10.1002/lt.20309.CrossRefGoogle Scholar
  58. 58.
    Chouchani, E. T., et al. (2016). A unifying mechanism for mitochondrial superoxide production during ischemia-reperfusion injury. Cell Metabolism, 23, 254–263. doi: 10.1016/j.cmet.2015.12.009.CrossRefPubMedGoogle Scholar
  59. 59.
    Quarrie, R., et al. (2014). Mitochondrial uncoupling does not decrease reactive oxygen species production after ischemia-reperfusion. American Journal of Physiology. Heart and Circulatory Physiology, 307, H996–h1004. doi: 10.1152/ajpheart.00189.2014.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Jaeschke, H., & Woolbright, B. L. (2012). Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species. Transplantation Reviews (Orlando, Fla.), 26, 103–114. doi: 10.1016/j.trre.2011.10.006.CrossRefGoogle Scholar
  61. 61.
    Murphy, M. P. (2009). How mitochondria produce reactive oxygen species. The Biochemical Journal, 417, 1–13. doi: 10.1042/bj20081386.CrossRefPubMedGoogle Scholar
  62. 62.
    St-Pierre, J., Buckingham, J. A., Roebuck, S. J., & Brand, M. D. (2002). Topology of superoxide production from different sites in the mitochondrial electron transport chain. The Journal of Biological Chemistry, 277, 44784–44790. doi: 10.1074/jbc.M207217200.CrossRefPubMedGoogle Scholar
  63. 63.
    Barja, G. (1999). Mitochondrial oxygen radical generation and leak: Sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. Journal of Bioenergetics and Biomembranes, 31, 347–366.CrossRefPubMedGoogle Scholar
  64. 64.
    Grivennikova, V. G., & Vinogradov, A. D. (2006). Generation of superoxide by the mitochondrial Complex I. Biochimica et Biophysica Acta, 1757, 553–561. doi: 10.1016/j.bbabio.2006.03.013.CrossRefPubMedGoogle Scholar
  65. 65.
    Kwong, L. K., & Sohal, R. S. (2000). Age-related changes in activities of mitochondrial electron transport complexes in various tissues of the mouse. Archives of Biochemistry and Biophysics, 373, 16–22. doi: 10.1006/abbi.1999.1495.CrossRefPubMedGoogle Scholar
  66. 66.
    Paradies, G., et al. (2004). Decrease in mitochondrial complex I activity in ischemic/reperfused rat heart: Involvement of reactive oxygen species and cardiolipin. Circulation Research, 94, 53–59. doi: 10.1161/01.res.0000109416.56608.64.CrossRefPubMedGoogle Scholar
  67. 67.
    Niatsetskaya, Z. V., et al. (2012). The oxygen free radicals originating from mitochondrial complex I contribute to oxidative brain injury following hypoxia-ischemia in neonatal mice. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 32, 3235–3244. doi: 10.1523/jneurosci.6303-11.2012.CrossRefGoogle Scholar
  68. 68.
    Paradies, G., et al. (1999). Lipid peroxidation and alterations to oxidative metabolism in mitochondria isolated from rat heart subjected to ischemia and reperfusion. Free Radical Biology & Medicine, 27, 42–50.CrossRefGoogle Scholar
  69. 69.
    Nakagawa, T., et al. (2005). Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature, 434, 652–658. doi: 10.1038/nature03317.CrossRefPubMedGoogle Scholar
  70. 70.
    Baines, C. P., et al. (2005). Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature, 434, 658–662. doi: 10.1038/nature03434.CrossRefPubMedGoogle Scholar
  71. 71.
    Schinzel, A. C., et al. (2005). Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proceedings of the National Academy of Sciences of the United States of America, 102, 12005–12010. doi: 10.1073/pnas.0505294102.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Broekemeier, K. M., Dempsey, M. E., & Pfeiffer, D. R. (1989). Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. The Journal of Biological Chemistry, 264, 7826–7830.PubMedGoogle Scholar
  73. 73.
    Waldmeier, P. C., Zimmermann, K., Qian, T., Tintelnot-Blomley, M., & Lemasters, J. J. (2003). Cyclophilin D as a drug target. Current Medicinal Chemistry, 10, 1485–1506.CrossRefPubMedGoogle Scholar
  74. 74.
    Halestrap, A. P., Connern, C. P., Griffiths, E. J., & Kerr, P. M. (1997). Cyclosporin A binding to mitochondrial cyclophilin inhibits the permeability transition pore and protects hearts from ischaemia/reperfusion injury. Molecular and Cellular Biochemistry, 174, 167–172.CrossRefPubMedGoogle Scholar
  75. 75.
    Warne, J., et al. (2016). Selective inhibition of the mitochondrial permeability transition pore protects against neurodegeneration in experimental multiple sclerosis. The Journal of Biological Chemistry, 291, 4356–4373. doi: 10.1074/jbc.M115.700385.CrossRefPubMedGoogle Scholar
  76. 76.
    Takeuchi, O., & Akira, S. (2010). Pattern recognition receptors and inflammation. Cell, 140, 805–820. doi: 10.1016/j.cell.2010.01.022.CrossRefPubMedGoogle Scholar
  77. 77.
    Tsung, A., et al. (2005). The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. The Journal of Experimental Medicine, 201, 1135–1143. doi: 10.1084/jem.20042614.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Lotze, M. T., et al. (2007). The grateful dead: Damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunological Reviews, 220, 60–81. doi: 10.1111/j.1600-065X.2007.00579.x.CrossRefPubMedGoogle Scholar
  79. 79.
    Hu, Q., Wood, C. R., Cimen, S., Venkatachalam, A. B., & Alwayn, I. P. (2015). Mitochondrial Damage-Associated Molecular Patterns (MTDs) are released during hepatic ischemia reperfusion and induce inflammatory responses. PLoS ONE, 10, e0140105. doi: 10.1371/journal.pone.0140105.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Zhang, Q., et al. (2010). Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature, 464, 104–107. doi: 10.1038/nature08780.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Krysko, D. V., et al. (2011). Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends in Immunology, 32, 157–164. doi: 10.1016/ Scholar
  82. 82.
    Ditonno, P., et al. (2013). Effects of ischemia-reperfusion injury in kidney transplantation: Risk factors and early and long-term outcomes in a single center. Transplantation Proceedings, 45, 2641–2644. doi: 10.1016/j.transproceed.2013.07.025.CrossRefPubMedGoogle Scholar
  83. 83.
    Yarlagadda, S. G., Coca, S. G., Formica, R. N., Jr., Poggio, E. D., & Parikh, C. R. (2009). Association between delayed graft function and allograft and patient survival: A systematic review and meta-analysis. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 24, 1039–1047. doi: 10.1093/ndt/gfn667.CrossRefGoogle Scholar
  84. 84.
    Krishnan, A. R., et al. (2016). Prolonged ischemic time, delayed graft function, graft and patient outcomes in live-donor kidney transplant recipients. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. doi: 10.1111/ajt.13817.CrossRefPubMedGoogle Scholar
  85. 85.
    Kayler, L. K., Srinivas, T. R., & Schold, J. D. (2011). Influence of CIT-induced DGF on kidney transplant outcomes. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 11, 2657–2664. doi: 10.1111/j.1600-6143.2011.03817.x.CrossRefGoogle Scholar
  86. 86.
    Wu, W. K., Famure, O., Li, Y., & Kim, S. J. (2015). Delayed graft function and the risk of acute rejection in the modern era of kidney transplantation. Kidney International, 88, 851–858. doi: 10.1038/ki.2015.190.CrossRefPubMedGoogle Scholar
  87. 87.
    Mikhalski, D., et al. (2008). Cold ischemia is a major determinant of acute rejection and renal graft survival in the modern era of immunosuppression. Transplantation, 85, S3–S9. doi: 10.1097/TP.0b013e318169c29e.CrossRefPubMedGoogle Scholar
  88. 88.
    Perez Valdivia, M. A., et al. (2011). Impact of cold ischemia time on initial graft function and survival rates in renal transplants from deceased donors performed in Andalusia. Transplantation Proceedings, 43, 2174–2176. doi: 10.1016/j.transproceed.2011.06.047.CrossRefPubMedGoogle Scholar
  89. 89.
    Salahudeen, A. K., Haider, N., & May, W. (2004). Cold ischemia and the reduced long-term survival of cadaveric renal allografts. Kidney International, 65, 713–718. doi: 10.1111/j.1523-1755.2004.00416.x.CrossRefPubMedGoogle Scholar
  90. 90.
    Roodnat, J. I., et al. (2003). Ischemia times and donor serum creatinine in relation to renal graft failure. Transplantation, 75, 799–804. doi: 10.1097/ Scholar
  91. 91.
    Debout, A., et al. (2015). Each additional hour of cold ischemia time significantly increases the risk of graft failure and mortality following renal transplantation. Kidney International, 87, 343–349. doi: 10.1038/ki.2014.304.CrossRefPubMedGoogle Scholar
  92. 92.
    Simpkins, C. E., et al. (2007). Cold ischemia time and allograft outcomes in live donor renal transplantation: Is live donor organ transport feasible? American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 7, 99–107. doi: 10.1111/j.1600-6143.2006.01597.x.CrossRefGoogle Scholar
  93. 93.
    Gill, J., Dong, J., Eng, M., Landsberg, D., & Gill, J. S. (2014). Pulsatile perfusion reduces the risk of delayed graft function in deceased donor kidney transplants, irrespective of donor type and cold ischemic time. Transplantation, 97, 668–674. doi: 10.1097/ Scholar
  94. 94.
    Schechter, M. A., et al. (2016). Elevated cardiac troponin I in preservation solution is associated with primary graft dysfunction. Journal of Cardiac Failure, 22, 158–162. doi: 10.1016/j.cardfail.2015.08.339.CrossRefPubMedGoogle Scholar
  95. 95.
    Chen, X. B., & Xu, M. Q. (2014). Primary graft dysfunction after liver transplantation. Hepatobiliary & Pancreatic Diseases International : HBPD INT, 13, 125–137.CrossRefGoogle Scholar
  96. 96.
    Grimm, J. C., et al. (2015). Association between prolonged graft ischemia and primary graft failure or survival following lung transplantation. JAMA Surgery, 150, 547–553. doi: 10.1001/jamasurg.2015.12.CrossRefPubMedGoogle Scholar
  97. 97.
    Fiser, S. M., et al. (2001). Influence of graft ischemic time on outcomes following lung transplantation. The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, 20, 1291–1296.CrossRefGoogle Scholar
  98. 98.
    King, R. C., et al. (2000). Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation. The Annals of Thoracic Surgery, 69, 1681–1685.CrossRefPubMedGoogle Scholar
  99. 99.
    Palmer, S. M., et al. (2005). Innate immunity influences long-term outcomes after human lung transplant. American Journal of Respiratory and Critical Care Medicine, 171, 780–785. doi: 10.1164/rccm.200408-1129OC.CrossRefPubMedGoogle Scholar
  100. 100.
    Palmer, S. M., et al. (2006). Donor polymorphisms in Toll-like receptor-4 influence the development of rejection after renal transplantation. Clinical Transplantation, 20, 30–36. doi: 10.1111/j.1399-0012.2005.00436.x.CrossRefPubMedGoogle Scholar
  101. 101.
    Imamura, T., et al. (2015). Late rejection occurred in recipients who experienced acute cellular rejection within the first year after heart transplantation. International Heart Journal, 56, 174–179. doi: 10.1536/ihj.14-187.CrossRefPubMedGoogle Scholar
  102. 102.
    Soderlund, C., et al. (2014). Acute cellular rejection the first year after heart transplantation and its impact on survival: A single-centre retrospective study at Skane University Hospital in Lund 1988-2010. Transplant International : Official Journal of the European Society for Organ Transplantation, 27, 482–492. doi: 10.1111/tri.12284.CrossRefGoogle Scholar
  103. 103.
    Kubo, S. H., et al. (1995). Risk factors for late recurrent rejection after heart transplantation: A multiinstitutional, multivariable analysis. Cardiac Transplant Research Database Group. The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, 14, 409–418.Google Scholar
  104. 104.
    Sharples, L. D., McNeil, K., Stewart, S., & Wallwork, J. (2002). Risk factors for bronchiolitis obliterans: A systematic review of recent publications. The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, 21, 271–281.CrossRefGoogle Scholar
  105. 105.
    Almond, P. S., et al. (1993). Risk factors for chronic rejection in renal allograft recipients. Transplantation, 55, 752–756.; discussion 756–757.CrossRefPubMedGoogle Scholar
  106. 106.
    Zhou, J. Q., et al. (2016). Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model. Acta cirurgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia, 31, 176–182. doi: 10.1590/s0102-865020160030000005.CrossRefGoogle Scholar
  107. 107.
    Janssen, H., Janssen, P. H., & Broelsch, C. E. (2003). Celsior solution compared with University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK) in the protection of human hepatocytes against ischemia-reperfusion injury. Transplant International : Official Journal of the European Society for Organ Transplantation, 16, 515–522. doi: 10.1007/s00147-003-0583-5.CrossRefGoogle Scholar
  108. 108.
    Zaouali, M. A., et al. (2014). Polyethylene glycol rinse solution: An effective way to prevent ischemia-reperfusion injury. World Journal of Gastroenterology, 20, 16203–16214. doi: 10.3748/wjg.v20.i43.16203.CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Faulds, D., Goa, K. L., & Benfield, P. (1993). Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs, 45, 953–1040.CrossRefPubMedGoogle Scholar
  110. 110.
    Patel, P., Patel, H., Panchal, S., & Mehta, T. (2012). Formulation strategies for drug delivery of tacrolimus: An overview. International Journal of Pharmaceutical Investigation, 2, 169–175. doi: 10.4103/2230-973X.106981.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Morelon, E., Mamzer-Bruneel, M. F., Peraldi, M. N., & Kreis, H. (2001). Sirolimus: A new promising immunosuppressive drug. Towards a rationale for its use in renal transplantation. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 16, 18–20.CrossRefGoogle Scholar
  112. 112.
    Thomas, K., Koelwel, C., Machei, U., Farber, L., & Gopferich, A. (2005). Three generations of cyclosporine a formulations: An in vitro comparison. Drug Development and Industrial Pharmacy, 31, 357–366. doi: 10.1081/DDC-54311.CrossRefPubMedGoogle Scholar
  113. 113.
    McAlister, V. C., Keshavamurthy, M., & Lee, T. D. (1999). Oral delivery of liposomal tacrolimus: Increased efficacy and reduced toxicity. Transplantation Proceedings, 31, 1110.CrossRefPubMedGoogle Scholar
  114. 114.
    Alemdar, A. Y., Sadi, D., McAlister, V. C., & Mendez, I. (2004). Liposomal formulations of tacrolimus and rapamycin increase graft survival and fiber outgrowth of dopaminergic grafts. Cell Transplantation, 13, 263–271.CrossRefPubMedGoogle Scholar
  115. 115.
    Ashok, B., Arleth, L., Hjelm, R. P., Rubinstein, I., & Onyuksel, H. (2004). In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization: Effects of PEG chain length and PC incorporation. Journal of Pharmaceutical Sciences, 93, 2476–2487. doi: 10.1002/jps.20150.CrossRefPubMedGoogle Scholar
  116. 116.
    Forrest, M. L., Won, C. Y., Malick, A. W., & Kwon, G. S. (2006). In vitro release of the mTOR inhibitor rapamycin from poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelles. Journal of Controlled Release: Official Journal of the Controlled Release Society, 110, 370–377. doi: 10.1016/j.jconrel.2005.10.008.CrossRefGoogle Scholar
  117. 117.
    Tang, L., et al. (2012). Immunosuppressive activity of size-controlled PEG-PLGA nanoparticles containing encapsulated cyclosporine A. Journal of Transplantation, 2012, 896141. doi: 10.1155/2012/896141.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Immordino, M. L., Dosio, F., & Cattel, L. (2006). Stealth liposomes: Review of the basic science, rationale, and clinical applications, existing and potential. International Journal of Nanomedicine, 1, 297–315.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Pinto-Alphandary, H., Andremont, A., & Couvreur, P. (2000). Targeted delivery of antibiotics using liposomes and nanoparticles: Research and applications. International Journal of Antimicrobial Agents, 13, 155–168.CrossRefPubMedGoogle Scholar
  120. 120.
    Brasnjevic, I., Steinbusch, H. W., Schmitz, C., Martinez-Martinez, P., & European NanoBioPharmaceutics Research, I. (2009). Delivery of peptide and protein drugs over the blood-brain barrier. Progress in Neurobiology, 87, 212–251. doi: 10.1016/j.pneurobio.2008.12.002.CrossRefPubMedGoogle Scholar
  121. 121.
    Chonn, A., Semple, S. C., & Cullis, P. R. (1992). Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes. The Journal of Biological Chemistry, 267, 18759–18765.PubMedGoogle Scholar
  122. 122.
    Senior, J., & Gregoriadis, G. (1982). Stability of small unilamellar liposomes in serum and clearance from the circulation: The effect of the phospholipid and cholesterol components. Life Sciences, 30, 2123–2136.CrossRefPubMedGoogle Scholar
  123. 123.
    Bae, Y. H., & Park, K. (2011). Targeted drug delivery to tumors: Myths, reality and possibility. Journal of Controlled Release: Official Journal of the Controlled Release Society, 153, 198–205. doi: 10.1016/j.jconrel.2011.06.001.CrossRefGoogle Scholar
  124. 124.
    Boerman, O. C., et al. (1995). Sterically stabilized liposomes labeled with indium-111 to image focal infection. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 36, 1639–1644.Google Scholar
  125. 125.
    Li, S. D., & Huang, L. (2008). Pharmacokinetics and biodistribution of nanoparticles. Molecular Pharmaceutics, 5, 496–504. doi: 10.1021/mp800049w.CrossRefPubMedGoogle Scholar
  126. 126.
    Price, M. E., Cornelius, R. M., & Brash, J. L. (2001). Protein adsorption to polyethylene glycol modified liposomes from fibrinogen solution and from plasma. Biochimica et Biophysica Acta, 1512, 191–205.CrossRefPubMedGoogle Scholar
  127. 127.
    Woodle, M. C., & Lasic, D. D. (1992). Sterically stabilized liposomes. Biochimica et Biophysica Acta, 1113, 171–199.CrossRefPubMedGoogle Scholar
  128. 128.
    Fukumura, D., & Jain, R. K. (2007). Tumor microvasculature and microenvironment: Targets for anti-angiogenesis and normalization. Microvascular Research, 74, 72–84. doi: 10.1016/j.mvr.2007.05.003.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Saha, R. N., Vasanthakumar, S., Bende, G., & Snehalatha, M. (2010). Nanoparticulate drug delivery systems for cancer chemotherapy. Molecular Membrane Biology, 27, 215–231. doi: 10.3109/09687688.2010.510804.CrossRefPubMedGoogle Scholar
  130. 130.
    Juillerat-Jeanneret, L. (2008). The targeted delivery of cancer drugs across the blood-brain barrier: Chemical modifications of drugs or drug-nanoparticles? Drug Discovery Today, 13, 1099–1106. doi: 10.1016/j.drudis.2008.09.005.CrossRefPubMedGoogle Scholar
  131. 131.
    Martuza, R. L. (1992). Molecular neurosurgery for glial and neuronal disorders. Stereotactic and Functional Neurosurgery, 59, 92–99.CrossRefPubMedGoogle Scholar
  132. 132.
    Okada, H., Okamoto, S., & Yoshida, J. (1994). [Gene therapy for brain tumors: cytokine gene therapy using DNA/liposome (series 3)]. No shinkei geka. Neurological Surgery, 22, 999–1004.PubMedGoogle Scholar
  133. 133.
    Sharma, U. S., Sharma, A., Chau, R. I., & Straubinger, R. M. (1997). Liposome-mediated therapy of intracranial brain tumors in a rat model. Pharmaceutical Research, 14, 992–998.CrossRefPubMedGoogle Scholar
  134. 134.
    Siegal, T., Horowitz, A., & Gabizon, A. (1995). Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: Biodistribution and therapeutic efficacy. Journal of Neurosurgery, 83, 1029–1037. doi: 10.3171/jns.1995.83.6.1029.CrossRefPubMedGoogle Scholar
  135. 135.
    Kakinuma, K., et al. (1996). Targeting chemotherapy for malignant brain tumor using thermosensitive liposome and localized hyperthermia. Journal of Neurosurgery, 84, 180–184. doi: 10.3171/jns.1996.84.2.0180.CrossRefPubMedGoogle Scholar
  136. 136.
    Nadig, S. N., et al. (2015). Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity. RSC Advances, 5, 43552–43562. doi: 10.1039/c5ra04057d.CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Ankola, D. D., Battisti, A., Solaro, R., & Kumar, M. N. (2010). Nanoparticles made of multi-block copolymer of lactic acid and ethylene glycol containing periodic side-chain carboxyl groups for oral delivery of cyclosporine A. Journal of the Royal Society, Interface / the Royal Society, 7 Suppl 4, S475–S481. doi: 10.1098/rsif.2010.0046.focus.CrossRefGoogle Scholar
  138. 138.
    Gref, R., et al. (2001). Development and characterization of CyA-loaded poly(lactic acid)-poly(ethylene glycol)PEG micro- and nanoparticles. Comparison with conventional PLA particulate carriers. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 51, 111–118.CrossRefGoogle Scholar
  139. 139.
    Italia, J. L., Bhatt, D. K., Bhardwaj, V., Tikoo, K., & Kumar, M. N. (2007). PLGA nanoparticles for oral delivery of cyclosporine: Nephrotoxicity and pharmacokinetic studies in comparison to Sandimmune Neoral. Journal of Controlled Release: Official Journal of the Controlled Release Society, 119, 197–206. doi: 10.1016/j.jconrel.2007.02.004.CrossRefGoogle Scholar
  140. 140.
    Lund, L. H., et al. (2013). The Registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Report--2013; focus theme: Age. The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, 32, 951–964. doi: 10.1016/j.healun.2013.08.006.CrossRefGoogle Scholar
  141. 141.
    Hollis, I. B., Reed, B. N., & Moranville, M. P. (2015). Medication management of cardiac allograft vasculopathy after heart transplantation. Pharmacotherapy, 35, 489–501. doi: 10.1002/phar.1580.CrossRefPubMedGoogle Scholar
  142. 142.
    Pober, J. S., Jane-wit, D., Qin, L., & Tellides, G. (2014). Interacting mechanisms in the pathogenesis of cardiac allograft vasculopathy. Arteriosclerosis, Thrombosis, and Vascular Biology, 34, 1609–1614. doi: 10.1161/atvbaha.114.302818.CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Khush, K. K., & Valantine, H. A. (2009). New developments in immunosuppressive therapy for heart transplantation. Expert Opinion on Emerging Drugs, 14, 1–21. doi: 10.1517/14728210902791605.CrossRefPubMedGoogle Scholar
  144. 144.
    Jane-Wit, D., et al. (2013). Alloantibody and complement promote T cell-mediated cardiac allograft vasculopathy through noncanonical nuclear factor-kappaB signaling in endothelial cells. Circulation, 128, 2504–2516. doi: 10.1161/circulationaha.113.002972.CrossRefPubMedGoogle Scholar
  145. 145.
    Photos, P. J., Bacakova, L., Discher, B., Bates, F. S., & Discher, D. E. (2003). Polymer vesicles in vivo: Correlations with PEG molecular weight. Journal of Controlled Release: Official Journal of the Controlled Release Society, 90, 323–334.CrossRefGoogle Scholar
  146. 146.
    Singh, B., Garg, T., Goyal, A. K., & Rath, G. (2014). Recent advancements in the cardiovascular drug carriers. Artificial Cells, Nanomedicine, and Biotechnology, 1–10. doi: 10.3109/21691401.2014.937868.CrossRefPubMedGoogle Scholar
  147. 147.
    Muralidharan, P., Mallory, E., Malapit, M., Hayes, D., Jr., & Mansour, H. M. (2014). Inhalable PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery as aerosolized colloidal dispersions and dry powder inhalers. Pharmaceutics, 6, 333–353. doi: 10.3390/pharmaceutics6020333.CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Danhier, F., Le Breton, A., & Preat, V. (2012). RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis. Molecular Pharmaceutics, 9, 2961–2973. doi: 10.1021/mp3002733.CrossRefPubMedGoogle Scholar
  149. 149.
    Muzykantov, V., & Muro, S. (2011). Targeting delivery of drugs in the vascular system. International Journal of Transport Phenomena, 12, 41–49.PubMedPubMedCentralGoogle Scholar
  150. 150.
    Franz, M., et al. (2015). Targeted delivery of interleukin-10 to chronic cardiac allograft rejection using a human antibody specific to the extra domain A of fibronectin. International Journal of Cardiology, 195, 311–322. doi: 10.1016/j.ijcard.2015.05.144.CrossRefPubMedGoogle Scholar
  151. 151.
    Franz, M., et al. (2014). De novo expression of fetal ED-A(+) fibronectin and B (+) tenascin-C splicing variants in human cardiac allografts: Potential impact for targeted therapy of rejection. Journal of Molecular Histology, 45, 519–532. doi: 10.1007/s10735-014-9573-4.CrossRefPubMedGoogle Scholar
  152. 152.
    Franz, M., et al. (2013). Selective imaging of chronic cardiac rejection using a human antibody specific to the alternatively spliced EDA domain of fibronectin. The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, 32, 641–650. doi: 10.1016/j.healun.2013.04.003.CrossRefGoogle Scholar
  153. 153.
    Raichlin, E., et al. (2007). Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. Circulation, 116, 2726–2733. doi: 10.1161/circulationaha.107.692996.CrossRefPubMedGoogle Scholar
  154. 154.
    Guo, Y., et al. (2012). Simultaneous diagnosis and gene therapy of immuno-rejection in rat allogeneic heart transplantation model using a T-cell-targeted theranostic nanosystem. ACS Nano, 6, 10646–10657. doi: 10.1021/nn3037573.CrossRefPubMedGoogle Scholar
  155. 155.
    Watts, A. B., Williams, R. O., 3rd, & Peters, J. I. (2009). Recent developments in drug delivery to prolong allograft survival in lung transplant patients. Drug Development and Industrial Pharmacy, 35, 259–271. doi: 10.1080/03639040802282904.CrossRefPubMedGoogle Scholar
  156. 156.
    Niven, R., et al. (2011). Safety and toxicology of cyclosporine in propylene glycol after 9-month aerosol exposure to beagle dogs. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 24, 205–212. doi: 10.1089/jamp.2010.0863.CrossRefPubMedGoogle Scholar
  157. 157.
    Wang, T., et al. (2007). Preclinical safety evaluation of inhaled cyclosporine in propylene glycol. Journal of Aerosol Medicine : The Official Journal of the International Society for Aerosols in Medicine, 20, 417–428. doi: 10.1089/jam.2007.0626.CrossRefGoogle Scholar
  158. 158.
    Iacono, A. T., et al. (2006). A randomized trial of inhaled cyclosporine in lung-transplant recipients. The New England Journal of Medicine, 354, 141–150. doi: 10.1056/NEJMoa043204.CrossRefPubMedGoogle Scholar
  159. 159.
    Johnson, B. A., et al. (2012). Cyclosporine inhalation solution does not improve bronchiolitis obliterans syndrome-free survival following lung transplant: Results from the CYCLIST trial. Journal of Heart and Lung Transplantation, 31, S66. doi: 10.1016/j.healun.2012.01.177.CrossRefGoogle Scholar
  160. 160.
    Corcoran, T. E., Niven, R., Verret, W., Dilly, S., & Johnson, B. A. (2014). Lung deposition and pharmacokinetics of nebulized cyclosporine in lung transplant patients. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 27, 178–184. doi: 10.1089/jamp.2013.1042.CrossRefPubMedPubMedCentralGoogle Scholar
  161. 161.
    Behr, J., et al. (2009). Lung deposition of a liposomal cyclosporine A inhalation solution in patients after lung transplantation. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 22, 121–130.CrossRefPubMedGoogle Scholar
  162. 162.
    Sato, H., et al. (2013). Development of cyclosporine A-loaded dry-emulsion formulation using highly purified glycerol monooleate for safe inhalation therapy. International Journal of Pharmaceutics, 448, 282–289. doi: 10.1016/j.ijpharm.2013.03.026.CrossRefPubMedGoogle Scholar
  163. 163.
    Carvalho, S. R., et al. (2014). Characterization and pharmacokinetic analysis of crystalline versus amorphous rapamycin dry powder via pulmonary administration in rats. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 88, 136–147. doi: 10.1016/j.ejpb.2014.05.008.CrossRefGoogle Scholar
  164. 164.
    Bayer, J., et al. (2013). Effect of inhaled tacrolimus on ischemia reperfusion injury in rat lung transplant model. The Journal of Thoracic and Cardiovascular Surgery, 146, 1213–1219.; discussion 1219. doi: 10.1016/j.jtcvs.2013.07.030.CrossRefPubMedGoogle Scholar
  165. 165.
    Heyder, J. (2004). Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proceedings of the American Thoracic Society, 1, 315–320. doi: 10.1513/pats.200409-046TA.CrossRefPubMedGoogle Scholar
  166. 166.
    Sung, J. C., Pulliam, B. L., & Edwards, D. A. (2007). Nanoparticles for drug delivery to the lungs. Trends in Biotechnology, 25, 563–570. doi: 10.1016/j.tibtech.2007.09.005.CrossRefPubMedGoogle Scholar
  167. 167.
    Cova, E., et al. (2015). Antibody-engineered nanoparticles selectively inhibit mesenchymal cells isolated from patients with chronic lung allograft dysfunction. Nanomedicine (London, England), 10, 9–23. doi: 10.2217/nnm.13.208.CrossRefGoogle Scholar
  168. 168.
    Salvadori, M., Rosso, G., & Bertoni, E. (2015). Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment. World Journal of Transplantation, 5, 52–67. doi: 10.5500/wjt.v5.i2.52.CrossRefPubMedPubMedCentralGoogle Scholar
  169. 169.
    Menke, J., Sollinger, D., Schamberger, B., Heemann, U., & Lutz, J. (2014). The effect of ischemia/reperfusion on the kidney graft. Current Opinion in Organ Transplantation, 19, 395–400. doi: 10.1097/mot.0000000000000090.CrossRefPubMedGoogle Scholar
  170. 170.
    Rogers, N. M., Stephenson, M. D., Kitching, A. R., Horowitz, J. D., & Coates, P. T. (2012). Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells. British Journal of Pharmacology, 166, 194–209. doi: 10.1111/j.1476-5381.2011.01590.x.CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    Hosgood, S. A., van Heurn, E., & Nicholson, M. L. (2015). Normothermic machine perfusion of the kidney: Better conditioning and repair? Transplant International : Official Journal of the European Society for Organ Transplantation, 28, 657–664. doi: 10.1111/tri.12319.CrossRefGoogle Scholar
  172. 172.
    Brat, A., Pol, R. A., & Leuvenink, H. G. (2015). Novel preservation methods to increase the quality of older kidneys. Current Opinion in Organ Transplantation, 20, 438–443. doi: 10.1097/mot.0000000000000215.CrossRefPubMedGoogle Scholar
  173. 173.
    O'Callaghan, J. M., Morgan, R. D., Knight, S. R., & Morris, P. J. (2013). Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes. The British Journal of Surgery, 100, 991–1001. doi: 10.1002/bjs.9169.CrossRefPubMedGoogle Scholar
  174. 174.
    Jiao, B., et al. (2013). Hypothermic machine perfusion reduces delayed graft function and improves one-year graft survival of kidneys from expanded criteria donors: A meta-analysis. PLoS ONE, 8, e81826. doi: 10.1371/journal.pone.0081826.CrossRefPubMedPubMedCentralGoogle Scholar
  175. 175.
    Brasile, L., Glowacki, P., Castracane, J., & Stubenitsky, B. M. (2010). Pretransplant kidney-specific treatment to eliminate the need for systemic immunosuppression. Transplantation, 90, 1294–1298. doi: 10.1097/TP.0b013e3181ffba97.CrossRefPubMedGoogle Scholar
  176. 176.
    Lobb, I., et al. (2015). Hydrogen sulfide treatment mitigates renal allograft ischemia reperfusion injury during cold storage and improves early transplant kidney function and survival following allogeneic renal transplantation. The Journal of Urology. doi: 10.1016/j.juro.2015.07.096.CrossRefPubMedGoogle Scholar
  177. 177.
    Thuillier, R., et al. (2014). Cyclodextrin curcumin formulation improves outcome in a preclinical pig model of marginal kidney transplantation. American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 14, 1073–1083. doi: 10.1111/ajt.12661.CrossRefGoogle Scholar
  178. 178.
    Pan, N., et al. (2015). Comparison of methods for the reconstruction of the hepatic artery in mouse orthotopic liver transplantation. PLoS ONE, 10, e0133030. doi: 10.1371/journal.pone.0133030.CrossRefPubMedPubMedCentralGoogle Scholar
  179. 179.
    Zhu, H., Yu, L., He, Y., & Wang, B. (2014). Nonhuman primate models of type 1 diabetes mellitus for islet transplantation. Journal of Diabetes Research, 785948. doi: 10.1155/2014/785948 (2014).
  180. 180.
    Chandra, P. K., et al. (2012). Inhibition of hepatitis C virus replication by intracellular delivery of multiple siRNAs by nanosomes. Molecular Therapy : The Journal of the American Society of Gene Therapy, 20, 1724–1736. doi: 10.1038/mt.2012.107.CrossRefGoogle Scholar
  181. 181.
    Kesharwani, P., Banerjee, S., Padhye, S., Sarkar, F. H., & Iyer, A. K. (2015). Parenterally administrable nano-micelles of 3,4-difluorobenzylidene curcumin for treating pancreatic cancer. Colloids and Surfaces. B, Biointerfaces, 132, 138–145. doi: 10.1016/j.colsurfb.2015.05.007.CrossRefPubMedGoogle Scholar
  182. 182.
    Kepsutlu, B., Nazli, C., Bal, T., & Kizilel, S. (2014). Design of bioartificial pancreas with functional micro/nano-based encapsulation of islets. Current Pharmaceutical Biotechnology, 15, 590–608.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Kunal J. Patel
    • 1
  • Carl Atkinson
    • 1
  • Ann-Marie Broome
    • 1
  • Satish N. Nadig
    • 1
    Email author
  1. 1.Medical University of South CarolinaCharlestonUSA

Personalised recommendations