Site Specific Controlled Release for Cardiovascular Disease: Translational Directions

  • Ilia Fishbein
  • Michael Chorny
  • Ivan S. Alferiev
  • Robert J. Levy
Chapter
Part of the Advances in Delivery Science and Technology book series (ADST)

Abstract

Cardiovascular diseases remain the leading cause of mortality worldwide. Despite tremendous progress in prophylaxis, diagnostics, and pharmacology of cardiovascular disorders, a number of disease states cannot be successfully treated even with the most sophisticated therapeutics. A significant part of the problem is a lack of adequate systems for the focal delivery of therapeutic agents to disease sites in the heart and blood vessels. Over the last 30 years, basic and translational research on the interface of pharmacology, pharmaceutics, physiology, biomaterials, and nanotechnology have made possible the emergence of clinical grade site specific controlled release devices, which have become standards of care in cardiovascular medicine. There are multiple advantages of controlled release systems for localized site specific treatments, including increased efficacy, reduced side effects, and favorable tissue scaffolding properties.

Keywords

Surfactant Catheter Convection Cobalt Biodegradation 

Notes

Acknowledgments

The authors thank Susan Kerns, the Children’s Hospital of Philadelphia, for her assistance in reviewing the manuscript and preparing materials for submission. The research at the Children’s Hospital of Philadelphia reported in this chapter was supported in part by a grant from the National Institutes of Health (HL72108), Scientist Development Grants from the American Heart Association, a QED-Grant from the University Science Center of Philadelphia, and The William J. Rashkind Endowment of The Children’s Hospital of Philadelphia.

References

  1. 1.
    Ellenbogen KA, Wood MA, Gilligan DM, Zmijewski M, Mans D (1999) Steroid eluting high impedance pacing leads decrease short and long-term current drain: results from a multicenter clinical trial. CapSure Z investigators. Pacing Clin Electrophysiol 22:39–48PubMedGoogle Scholar
  2. 2.
    Daemen J, Serruys PW (2007) Drug-eluting stent update 2007: part I. A survey of current and future generation drug-eluting stents: meaningful advances or more of the same? Circulation 116:316–328PubMedGoogle Scholar
  3. 3.
    Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, Kukreja N, Juni P, Sianos G, Hellige G, van Domburg RT, Hess OM, Boersma E, Meier B, Windecker S, Serruys PW (2007) Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet 369:667–678PubMedGoogle Scholar
  4. 4.
    Garg S, Serruys PW (2010) Coronary stents: looking forward. J Am Coll Cardiol 56:S43–S78PubMedGoogle Scholar
  5. 5.
    Garg S, Serruys PW (2010) Coronary stents: current status. J Am Coll Cardiol 56:S1–S42PubMedGoogle Scholar
  6. 6.
    Sousa JE, Serruys PW, Costa MA (2003) New frontiers in cardiology: drug-eluting stents: Part I. Circulation 107:2274–2279PubMedGoogle Scholar
  7. 7.
    Balakrishnan B, Dooley JF, Kopia G, Edelman ER (2007) Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution. J Control Release 123:100–108PubMedGoogle Scholar
  8. 8.
    Ranade SV, Miller KM, Richard RE, Chan AK, Allen MJ, Helmus MN (2004) Physical characterization of controlled release of paclitaxel from the TAXUS Express2 drug-eluting stent. J Biomed Mater Res A 71:625–634PubMedGoogle Scholar
  9. 9.
    Acharya G, Park K (2006) Mechanisms of controlled drug release from drug-eluting stents. Adv Drug Deliv Rev 58:387–401PubMedGoogle Scholar
  10. 10.
    Yang C, Burt HM (2006) Drug-eluting stents: factors governing local pharmacokinetics. Adv Drug Deliv Rev 58:402–411PubMedGoogle Scholar
  11. 11.
    McGinty S, McKee S, Wadsworth RM, McCormick C (2011) Modelling drug-eluting stents. Math Med Biol 28(1):1–29PubMedGoogle Scholar
  12. 12.
    Pontrelli G, de Monte P (2009) Modeling of mass dynamics in arterial drug-eluting stents. J Porous Media 12:19–28Google Scholar
  13. 13.
    Balakrishnan B, Dooley J, Kopia G, Edelman ER, Dooley JF, Tzafriri AR, Seifert P, Groothuis A, Rogers C (2008) Thrombus causes fluctuations in arterial drug delivery from intravascular stents. J Control Release 131:173–180PubMedGoogle Scholar
  14. 14.
    Balakrishnan B, Tzafriri AR, Seifert P, Groothuis A, Rogers C, Edelman ER (2005) Strut position, blood flow, and drug deposition: implications for single and overlapping drug-eluting stents. Circulation 111:2958–2965PubMedGoogle Scholar
  15. 15.
    O’Connell BM, McGloughlin TM, Walsh MT (2010) Factors that affect mass transport from drug eluting stents into the artery wall. Biomed Eng Online 9:15PubMedGoogle Scholar
  16. 16.
    Hwang CW, Wu D, Edelman ER (2003) Impact of transport and drug properties on the local pharmacology of drug-eluting stents. Int J Cardiovasc Intervent 5(1):7–12PubMedGoogle Scholar
  17. 17.
    Hwang CW, Wu D, Edelman ER (2001) Physiological transport forces govern drug distribution for stent-based delivery. Circulation 104(5):600–605PubMedGoogle Scholar
  18. 18.
    Hwang CW, Levin AD, Jonas M, Li PH, Edelman ER (2005) Thrombosis modulates arterial drug distribution for drug-eluting stents. Circulation 111:1619–1626PubMedGoogle Scholar
  19. 19.
    Tzafriri AR, Vukmirovic N, Kolachalama VB, Astafieva I, Edelman ER (2010) Lesion complexity determines arterial drug distribution after local drug delivery. J Control Release 142:332–338PubMedGoogle Scholar
  20. 20.
    Wessely R (2010) New drug-eluting stent concepts. Nat Rev Cardiol 7:194–203PubMedGoogle Scholar
  21. 21.
    Pache J, Kastrati A, Mehilli J, Schuhlen H, Dotzer F, Hausleiter J, Fleckenstein M, Neumann FJ, Sattelberger U, Schmitt C, Muller M, Dirschinger J, Schomig A (2003) Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO-2) trial. J Am Coll Cardiol 41:1283–1288PubMedGoogle Scholar
  22. 22.
    Chorny M, Fishbein I, Yellen BB, Alferiev IS, Bakay M, Ganta S, Adamo R, Amiji M, Friedman G, Levy RJ (2010) Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc Natl Acad Sci USA 107:8346–8351PubMedGoogle Scholar
  23. 23.
    Ormiston JA, Abizaid A, Spertus J, Fajadet J, Mauri L, Schofer J, Verheye S, Dens J, Thuesen L, Dubois C, Hoffmann R, Wijns W, Fitzgerald PJ, Popma JJ, Macours N, Cebrian A, Stoll HP, Rogers C, Spaulding C (2010) Six-month results of the NEVO RES-ELUTION I (NEVO RES-I) Trial: a randomized, multicenter comparison of the NEVO Sirolimus-eluting coronary stent with the TAXUS Liberte Paclitaxel-eluting stent in de novo native coronary artery lesions. Circ Cardiovasc Interv 3:556–564PubMedGoogle Scholar
  24. 24.
    Granada JF, Inami S, Aboodi MS, Tellez A, Milewski K, Wallace-Bradley D, Parker S, Rowland S, Nakazawa G, Vorpahl M, Kolodgie FD, Kaluza GL, Leon MB, Virmani R (2010) Development of a novel prohealing stent designed to deliver sirolimus from a biodegradable abluminal matrix. Circ Cardiovasc Interv 3:257–266PubMedGoogle Scholar
  25. 25.
    Tamai H, Igaki K, Kyo E, Kosuga K, Kawashima A, Matsui S, Komori H, Tsuji T, Motohara S, Uehata H (2000) Initial and 6-month results of biodegradable poly-l-lactic acid coronary stents in humans. Circulation 102:399–404PubMedGoogle Scholar
  26. 26.
    Perlstein I, Connolly JM, Cui X, Song C, Li Q, Jones PL, Lu Z, DeFelice S, Klugherz B, Wilensky R, Levy RJ (2003) DNA delivery from an intravascular stent with a denatured collagen-polylactic-polyglycolic acid-controlled release coating: mechanisms of enhanced transfection. Gene Ther 10:1420–1428PubMedGoogle Scholar
  27. 27.
    Williams DO, Abbott JD, Kip KE (2006) Outcomes of 6906 patients undergoing percutaneous coronary intervention in the era of drug-eluting stents: report of the DEScover Registry. Circulation 114:2154–2162PubMedGoogle Scholar
  28. 28.
    Virmani R, Farb A, Guagliumi G, Kolodgie FD (2004) Drug-eluting stents: caution and concerns for long-term outcome. Coron Artery Dis 15:313–318PubMedGoogle Scholar
  29. 29.
    van der Giessen WJ, Lincoff AM, Schwartz RS, van Beusekom HM, Serruys PW, Holmes DR Jr, Ellis SG, Topol EJ (1996) Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation 94:1690–1697PubMedGoogle Scholar
  30. 30.
    Appleby CE, Kingston PA (2004) Gene therapy for restenosis–what now, what next? Curr Gene Ther 4:153–182PubMedGoogle Scholar
  31. 31.
    Walter DH, Cejna M, Diaz-Sandoval L, Willis S, Kirkwood L, Stratford PW, Tietz AB, Kirchmair R, Silver M, Curry C, Wecker A, Yoon YS, Heidenreich R, Hanley A, Kearney M, Tio FO, Kuenzler P, Isner JM, Losordo DW (2004) Local gene transfer of phVEGF-2 plasmid by gene-eluting stents. An alternative strategy for inhibition of restenosis. Circulation 110:36–45PubMedGoogle Scholar
  32. 32.
    Gaffney MM, Hynes SO, Barry F, O’Brien T (2007) Cardiovascular gene therapy: current status and therapeutic potential. Br J Pharmacol 152:175–188PubMedGoogle Scholar
  33. 33.
    Rissanen TT, Yla-Herttuala S (2007) Current status of cardiovascular gene therapy. Mol Ther 15:1233–1247PubMedGoogle Scholar
  34. 34.
    Roks AJ, Henning RH, Buikema H, Pinto YM, Kraak MJ, Tio RA, de Zeeuw D, Haisma HJ, Wilschut J, van Gilst WH (2002) Recombinant Semliki Forest virus as a vector system for fast and selective in vivo gene delivery into balloon-injured rat aorta. Gene Ther 9:95–101PubMedGoogle Scholar
  35. 35.
    Kotani H, Nakajima T, Lai S, Morishita R, Kaneda Y (2004) The HVJ-envelope as an innovative vector system for cardiovascular disease. Curr Gene Ther 4:183–194PubMedGoogle Scholar
  36. 36.
    Sharif F, Daly K, Crowley J, O’Brien T (2004) Current status of catheter- and stent-based gene therapy. Cardiovasc Res 64:208–216PubMedGoogle Scholar
  37. 37.
    Laitinen M, Hartikainen J, Hiltunen MO, Eranen J, Kiviniemi M, Narvanen O, Makinen K, Manninen H, Syvanne M, Martin JF, Laakso M, Yla-Herttuala S (2000) Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Hum Gene Ther 11:263–270PubMedGoogle Scholar
  38. 38.
    von der Leyen HE, Muegge A, Hanefeld C, Hamm CW, Rau M, Rupprecht HJ, Zeiher AM, Fichtlscherer S (2010) A prospective, single-blind, multicenter, dose escalation study of intracoronary iNOS lipoplex (CAR-MP583) gene therapy for the prevention of restenosis in patients with de novo or restenotic coronary artery lesion (REGENT I Extension). Hum Gene Ther 18:18Google Scholar
  39. 39.
    Versari D, Lerman LO, Lerman A (2007) The importance of reendothelialization after arterial injury. Curr Pharm Des 13:1811–1824PubMedGoogle Scholar
  40. 40.
    Flugelman MY, Virmani R, Leon MB, Bowman RL, Dichek DA (1992) Genetically engineered endothelial cells remain adherent and viable after stent deployment and exposure to flow in vitro. Circ Res 70:348–354PubMedGoogle Scholar
  41. 41.
    Scott NA, Candal FJ, Robinson KA, Ades EW (1995) Seeding of intracoronary stents with immortalized human microvascular endothelial cells. Am Heart J 129:860–866PubMedGoogle Scholar
  42. 42.
    Berinyi LK, Conte MS, Mulligan RC (1992) Repopulation of injured arteries with genetically modified endothelial cells. J Vasc Surg 15:932–934PubMedGoogle Scholar
  43. 43.
    Thompson MM, Budd JS, Eady SL, Hartley G, Early M, James RF, Bell PR (1994) Platelet deposition after angioplasty is abolished by restoration of the endothelial cell monolayer. J Vasc Surg 19:478–486PubMedGoogle Scholar
  44. 44.
    Gulati R, Jevremovic D, Peterson TE, Witt TA, Kleppe LS, Mueske CS, Lerman A, Vile RG, Simari RD (2003) Autologous culture-modified mononuclear cells confer vascular protection after arterial injury. Circulation 108:1520–1526PubMedGoogle Scholar
  45. 45.
    Gulati R, Jevremovic D, Witt TA, Kleppe LS, Vile RG, Lerman A, Simari RD (2004) Modulation of the vascular response to injury by autologous blood-derived outgrowth endothelial cells. Am J Physiol Heart Circ Physiol 287:H512–H517PubMedGoogle Scholar
  46. 46.
    Werner N, Junk S, Laufs U, Link A, Walenta K, Bohm M, Nickenig G (2003) Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res 93:e17–e24PubMedGoogle Scholar
  47. 47.
    He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZS (2004) Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke 35:2378–2384PubMedGoogle Scholar
  48. 48.
    Gulati R, Simari RD (2004) Autologous cell-based therapies for vascular disease. Trends Cardiovasc Med 14:262–267PubMedGoogle Scholar
  49. 49.
    Kipshidze N, Dangas G, Tsapenko M, Moses J, Leon MB, Kutryk M, Serruys P (2004) Role of the endothelium in modulating neointimal formation: vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions. J Am Coll Cardiol 44:733–739PubMedGoogle Scholar
  50. 50.
    Aoki J, Serruys PW, van Beusekom H, Ong AT, McFadden EP, Sianos G, van der Giessen WJ, Regar E, de Feyter PJ, Davis HR, Rowland S, Kutryk MJ (2005) Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry. J Am Coll Cardiol 45:1574–1579PubMedGoogle Scholar
  51. 51.
    Schober A, Hoffmann R, Opree N, Knarren S, Iofina E, Hutschenreuter G, Hanrath P, Weber C (2005) Peripheral CD34+ cells and the risk of in-stent restenosis in patients with coronary heart disease. Am J Cardiol 96:1116–1122PubMedGoogle Scholar
  52. 52.
    Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, Pratt RE, Mulligan RC, Dzau VJ (2003) Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy. Circulation 108:2710–2715PubMedGoogle Scholar
  53. 53.
    Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, Liew CC, Pratt RE, Dzau VJ (2004) Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation 109:1769–1775PubMedGoogle Scholar
  54. 54.
    Andres V (2004) Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential. Cardiovasc Res 63:11–21PubMedGoogle Scholar
  55. 55.
    Charron T, Nili N, Strauss BH (2006) The cell cycle: A critical therapeutic target to prevent vascular proliferative disease. Can J Cardiol 22(Suppl B):41B–55BPubMedGoogle Scholar
  56. 56.
    Schober A (2008) Chemokines in vascular dysfunction and remodeling. Arterioscler Thromb Vasc Biol 28:1950–1959PubMedGoogle Scholar
  57. 57.
    Levitzki A (2005) PDGF receptor kinase inhibitors for the treatment of restenosis. Cardiovasc Res 65:581–586PubMedGoogle Scholar
  58. 58.
    Banai S, Gertz SD, Gavish L, Chorny M, Perez LS, Lazarovichi G, Ianculuvich M, Hoffmann M, Orlowski M, Golomb G, Levitzki A (2004) Tyrphostin AGL-2043 eluting stent reduces neointima formation in porcine coronary arteries. Cardiovasc Res 64:165–171PubMedGoogle Scholar
  59. 59.
    Banai S, Wolf Y, Golomb G, Pearle A, Waltenberger J, Fishbein I, Schneider A, Gazit A, Perez L, Huber R, Lazarovichi G, Rabinovich L, Levitzki A, Gertz SD (1998) PDGF-receptor tyrosine kinase blocker AG1295 selectively attenuates smooth muscle cell growth in vitro and reduces neointimal formation after balloon angioplasty in swine. Circulation 97:1960–1969PubMedGoogle Scholar
  60. 60.
    Fishbein I, Waltenberger J, Banai S, Rabinovich L, Chorny M, Levitzki A, Gazit A, Huber R, Mayr U, Gertz SD, Golomb G (2000) Local delivery of platelet-derived growth factor receptor-specific tyrphostin inhibits neointimal formation in rats. Arterioscler Thromb Vasc Biol 20:667–676PubMedGoogle Scholar
  61. 61.
    Golomb G, Fishbein I, Banai S, Mishaly D, Moscovitz D, Gertz SD, Gazit A, Poradosu E, Levitzki A (1996) Controlled delivery of a tyrphostin inhibits intimal hyperplasia in a rat carotid artery injury model. Atherosclerosis 125:171–182PubMedGoogle Scholar
  62. 62.
    Giese NA, Marijianowski MM, McCook O, Hancock A, Ramakrishnan V, Fretto LJ, Chen C, Kelly AB, Koziol JA, Wilcox JN, Hanson SR (1999) The role of alpha and beta platelet-derived growth factor receptor in the vascular response to injury in nonhuman primates. Arterioscler Thromb Vasc Biol 19:900–909PubMedGoogle Scholar
  63. 63.
    Stefanadis C, Toutouzas K, Stefanadi E, Lazaris A, Patsouris E, Kipshidze N (2007) Inhibition of plaque neovascularization and intimal hyperplasia by specific targeting vascular endothelial growth factor with bevacizumab-eluting stent: an experimental study. Atherosclerosis 195:269–276PubMedGoogle Scholar
  64. 64.
    Wolf YG, Rasmussen LM, Ruoslahti E (1994) Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia in a rat model. J Clin Invest 93:1172–1178PubMedGoogle Scholar
  65. 65.
    Schober A, Knarren S, Lietz M, Lin EA, Weber C (2003) Crucial role of stromal cell-derived factor-1alpha in neointima formation after vascular injury in apolipoprotein E-deficient mice. Circulation 108:2491–2497PubMedGoogle Scholar
  66. 66.
    Wang CH, Anderson N, Li SH, Szmitko PE, Cherng WJ, Fedak PW, Fazel S, Li RK, Yau TM, Weisel RD, Stanford WL, Verma S (2006) Stem cell factor deficiency is vasculoprotective: unraveling a new therapeutic potential of imatinib mesylate. Circ Res 99:617–625PubMedGoogle Scholar
  67. 67.
    Yin X, Yutani C, Ikeda Y, Enjyoji K, Ishibashi-Ueda H, Yasuda S, Tsukamoto Y, Nonogi H, Kaneda Y, Kato H (2002) Tissue factor pathway inhibitor gene delivery using HVJ-AVE liposomes markedly reduces restenosis in atherosclerotic arteries. Cardiovasc Res 56:454–463PubMedGoogle Scholar
  68. 68.
    Levonen AL, Vahakangas E, Koponen JK, Yla-Herttuala S (2008) Antioxidant gene therapy for cardiovascular disease: current status and future perspectives. Circulation 117:2142–2150PubMedGoogle Scholar
  69. 69.
    Klugherz BD, Jones PL, Cui X, Chen W, Meneveau NF, DeFelice S, Connolly J, Wilensky RL, Levy RJ (2000) Gene delivery from a DNA controlled-release stent in porcine coronary arteries. Nat Biotechnol 18:1181–1184PubMedGoogle Scholar
  70. 70.
    Klugherz BD, Song C, DeFelice S, Cui X, Lu Z, Connolly J, Hinson JT, Wilensky RL, Levy RJ (2002) Gene delivery to pig coronary arteries from stents carrying antibody-tethered adenovirus. Hum Gene Ther 13:443–454PubMedGoogle Scholar
  71. 71.
    Johnson TW, Wu YX, Herdeg C, Baumbach A, Newby AC, Karsch KR, Oberhoff M, Johnson T, Karsch KK (2005) Stent-based delivery of tissue inhibitor of metalloproteinase-3 adenovirus inhibits neointimal formation in porcine coronary arteries. Arterioscler Thromb Vasc Biol 25:754–759PubMedGoogle Scholar
  72. 72.
    Sharif F, Hynes SO, McMahon J, Cooney R, Conroy S, Dockery P, Duffy G, Daly K, Crowley J, Bartlett JS, O’Brien T (2006) Gene-eluting stents: comparison of adenoviral and adeno- associated viral gene delivery to the blood vessel wall in vivo. Hum Gene Ther 17:741–750PubMedGoogle Scholar
  73. 73.
    Takahashi A, Palmer-Opolski M, Smith RC, Walsh K (2003) Transgene delivery of plasmid DNA to smooth muscle cells and macrophages from a biostable polymer-coated stent. Gene Ther 10:1471–1478PubMedGoogle Scholar
  74. 74.
    Carter AJ, Aggarwal M, Kopia GA, Tio F, Tsao PS, Kolata R, Yeung AC, Llanos G, Dooley J, Falotico R (2004) Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model. Cardiovasc Res 63:617–624PubMedGoogle Scholar
  75. 75.
    Sirois MG, Simons M, Kuter DJ, Rosenberg RD, Edelman ER (1997) Rat arterial wall retains myointimal hyperplastic potential long after arterial injury. Circulation 96:1291–1298PubMedGoogle Scholar
  76. 76.
    Ohtani K, Egashira K, Nakano K, Zhao G, Funakoshi K, Ihara Y, Kimura S, Tominaga R, Morishita R, Sunagawa K (2006) Stent-based local delivery of nuclear factor-kappaB decoy attenuates in-stent restenosis in hypercholesterolemic rabbits. Circulation 114:2773–2779PubMedGoogle Scholar
  77. 77.
    Fishbein I, Alferiev IS, Nyanguile O, Gaster R, Vohs JM, Wong GS, Felderman H, Chen IW, Choi H, Wilensky RL, Levy RJ (2006) Bisphosphonate-mediated gene vector delivery from the metal surfaces of stents. Proc Natl Acad Sci USA 103:159–164PubMedGoogle Scholar
  78. 78.
    Fishbein I, Alferiev I, Bakay M, Stachelek SJ, Sobolewski P, Lai M, Choi H, Chen IW, Levy RJ (2008) Local delivery of gene vectors from bare-metal stents by use of a biodegradable synthetic complex inhibits in-stent restenosis in rat carotid arteries. Circulation 117:2096–2103PubMedGoogle Scholar
  79. 79.
    Godin B, Sakamoto JH, Serda RE, Grattoni A, Bouamrani A, Ferrari M (2010) Emerging applications of nanomedicine for the diagnosis and treatment of cardiovascular diseases. Trends Pharmacol Sci 31:199–205PubMedGoogle Scholar
  80. 80.
    Strebhardt K, Ullrich A (2008) Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat Rev Cancer 8:473–480PubMedGoogle Scholar
  81. 81.
    Umashankar PR, Hari PR, Sreenivasan K (2009) Effect of blood flow on drug release from DES: an experimental study. Int J Cardiol 131:415–417PubMedGoogle Scholar
  82. 82.
    Chorny M, Fishbein I, Danenberg HD, Golomb G (2002) Lipophilic drug loaded nanospheres prepared by nanoprecipitation: effect of formulation variables on size, drug recovery and release kinetics. J Control Release 83:389–400PubMedGoogle Scholar
  83. 83.
    Chorny M, Fishbein I, Golomb G (2000) Drug delivery systems for the treatment of restenosis. Crit Rev Ther Drug Carrier Syst 17:249–284PubMedGoogle Scholar
  84. 84.
    Feng SS, Zeng W, Teng Lim Y, Zhao L, Yin Win K, Oakley R, Hin Teoh S, Hang Lee RC, Pan S (2007) Vitamin E TPGS-emulsified poly(lactic-co-glycolic acid) nanoparticles for cardiovascular restenosis treatment. Nanomedicine (Lond) 2:333–344Google Scholar
  85. 85.
    Klugherz BD, Meneveau N, Chen W, Wade-Whittaker F, Papandreou G, Levy R, Wilensky RL (1999) Sustained intramural retention and regional redistribution following local vascular delivery of polylactic-coglycolic acid and liposomal nanoparticulate formulations containing probucol. J Cardiovasc Pharmacol Ther 4:167–174PubMedGoogle Scholar
  86. 86.
    Westedt U, Kalinowski M, Wittmar M, Merdan T, Unger F, Fuchs J, Schaller S, Bakowsky U, Kissel T (2007) Poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) nanoparticles for local delivery of paclitaxel for restenosis treatment. J Control Release 119:41–51PubMedGoogle Scholar
  87. 87.
    Zweers ML, Engbers GH, Grijpma DW, Feijen J (2006) Release of anti-restenosis drugs from poly(ethylene oxide)-poly(DL-lactic-co-glycolic acid) nanoparticles. J Control Release 114:317–324PubMedGoogle Scholar
  88. 88.
    Deshpande D, Devalapally H, Amiji M (2008) Enhancement in anti-proliferative effects of paclitaxel in aortic smooth muscle cells upon co-administration with ceramide using biodegradable polymeric nanoparticles. Pharm Res 25:1936–1947PubMedGoogle Scholar
  89. 89.
    Kolodgie FD, John M, Khurana C, Farb A, Wilson PS, Acampado E, Desai N, Soon-Shiong P, Virmani R (2002) Sustained reduction of in-stent neointimal growth with the use of a novel systemic nanoparticle paclitaxel. Circulation 106:1195–1198PubMedGoogle Scholar
  90. 90.
    Reddy MK, Vasir JK, Sahoo SK, Jain TK, Yallapu MM, Labhasetwar V (2008) Inhibition of apoptosis through localized delivery of rapamycin-loaded nanoparticles prevented neointimal hyperplasia and reendothelialized injured artery. Circ Cardiovasc Interv 1:209–216PubMedGoogle Scholar
  91. 91.
    Cyrus T, Zhang H, Allen JS, Williams TA, Hu G, Caruthers SD, Wickline SA, Lanza GM (2008) Intramural delivery of rapamycin with alphavbeta3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury. Arterioscler Thromb Vasc Biol 28:820–826PubMedGoogle Scholar
  92. 92.
    Joner M, Morimoto K, Kasukawa H, Steigerwald K, Merl S, Nakazawa G, John MC, Finn AV, Acampado E, Kolodgie FD, Gold HK, Virmani R (2008) Site-specific targeting of nanoparticle prednisolone reduces in-stent restenosis in a rabbit model of established atheroma. Arterioscler Thromb Vasc Biol 28:1960–1966PubMedGoogle Scholar
  93. 93.
    Fishbein I, Chorny M, Banai S, Levitzki A, Danenberg HD, Gao J, Chen X, Moerman E, Gati I, Goldwasser V, Golomb G (2001) Formulation and delivery mode affect disposition and activity of tyrphostin-loaded nanoparticles in the rat carotid model. Arterioscler Thromb Vasc Biol 21:1434–1439PubMedGoogle Scholar
  94. 94.
    Westedt U, Barbu-Tudoran L, Schaper AK, Kalinowski M, Alfke H, Kissel T (2002) Deposition of nanoparticles in the arterial vessel by porous balloon catheters: localization by confocal laser scanning microscopy and transmission electron microscopy. AAPS PharmSci 4:E41PubMedGoogle Scholar
  95. 95.
    Uwatoku T, Shimokawa H, Abe K, Matsumoto Y, Hattori T, Oi K, Matsuda T, Kataoka K, Takeshita A (2003) Application of nanoparticle technology for the prevention of restenosis after balloon injury in rats. Circ Res 92:e62–e69PubMedGoogle Scholar
  96. 96.
    Labhasetwar V, Song C, Humphrey W, Shebuski R, Levy RJ (1998) Arterial uptake of biodegradable nanoparticles: effect of surface modifications. J Pharm Sci 87:1229–1234PubMedGoogle Scholar
  97. 97.
    Zou W, Cao G, Xi Y, Zhang N (2009) New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles. Drug Deliv 16:15–23PubMedGoogle Scholar
  98. 98.
    Chan JM, Zhang L, Tong R, Ghosh D, Gao W, Liao G, Yuet KP, Gray D, Rhee JW, Cheng J, Golomb G, Libby P, Langer R, Farokhzad OC (2010) Spatiotemporal controlled delivery of nanoparticles to injured vasculature. Proc Natl Acad Sci USA 107:2213–2218PubMedGoogle Scholar
  99. 99.
    Michon IN, Hauer AD, von der Thusen JH, Molenaar TJ, van Berkel TJ, Biessen EA, Kuiper J (2002) Targeting of peptides to restenotic vascular smooth muscle cells using phage display in vitro and in vivo. Biochim Biophys Acta 1591:87–97PubMedGoogle Scholar
  100. 100.
    Nah JW, Yu L, Han S, Ahn CH, Kim SW (2002) Artery wall binding peptide-poly(ethylene glycol)-grafted-poly(L-lysine)-based gene delivery to artery wall cells. J Control Release 78:273–284PubMedGoogle Scholar
  101. 101.
    Olsson U, Camejo G, Hurt-Camejo E, Elfsber K, Wiklund O, Bondjers G (1997) Possible functional interactions of apolipoprotein B-100 segment that associate with cell proteoglycans and the apoB/E receptor. Arterioscler Thromb Vasc Biol 17:149–155PubMedGoogle Scholar
  102. 102.
    Hamilton AJ, Huang SL, Warnick D, Rabbat M, Kane B, Nagaraj A, Klegerman M, McPherson DD (2004) Intravascular ultrasound molecular imaging of atheroma components in vivo. J Am Coll Cardiol 43:453–460PubMedGoogle Scholar
  103. 103.
    Danenberg HD, Fishbein I, Gao J, Monkkonen J, Reich R, Gati I, Moerman E, Golomb G, Cohen-Sela E, Rosenzweig O, Epstein H (2002) Macrophage depletion by clodronate-containing liposomes reduces neointimal formation after balloon injury in rats and rabbits. Circulation 106:599–605PubMedGoogle Scholar
  104. 104.
    Cohen-Sela E, Rosenzweig O, Gao J, Epstein H, Gati I, Reich R, Danenberg HD, Golomb G (2006) Alendronate-loaded nanoparticles deplete monocytes and attenuate restenosis. J Control Release 113:23–30PubMedGoogle Scholar
  105. 105.
    Welt FG, Rogers C (2002) Inflammation and restenosis in the stent era. Arterioscler Thromb Vasc Biol 22:1769–1776PubMedGoogle Scholar
  106. 106.
    Takeshita S, Gal D, Leclerc G, Pickering JG, Riessen R, Weir L, Isner JM (1994) Increased gene expression after liposome-mediated arterial gene transfer associated with intimal smooth muscle cell proliferation. In vitro and in vivo findings in a rabbit model of vascular injury. J Clin Invest 93:652–661PubMedGoogle Scholar
  107. 107.
    Riessen R, Rahimizadeh H, Blessing E, Takeshita S, Barry JJ, Isner JM (1993) Arterial gene transfer using pure DNA applied directly to a hydrogel-coated angioplasty balloon. Hum Gene Ther 4:749–758PubMedGoogle Scholar
  108. 108.
    Muhs A, Heublein B, Schletter J, Herrmann A, Rudiger M, Sturm M, Grust A, Malms J, Schrader J, Von Der Leyen HE (2003) Preclinical evaluation of inducible nitric oxide synthase lipoplex gene therapy for inhibition of stent-induced vascular neointimal lesion formation. Hum Gene Ther 14:375–383PubMedGoogle Scholar
  109. 109.
    Abbas AO, Donovan MD, Salem AK (2008) Formulating poly(lactide-co-glycolide) particles for plasmid DNA delivery. J Pharm Sci 97:2448–2461PubMedGoogle Scholar
  110. 110.
    Yang J, Zeng Y, Li Y, Song C, Zhu W, Guan H, Li X (2008) Intravascular site-specific delivery of a therapeutic antisense for the inhibition of restenosis. Eur J Pharm Sci 35:427–434PubMedGoogle Scholar
  111. 111.
    Cohen H, Levy RJ, Gao J, Fishbein I, Kousaev V, Sosnowski S, Slomkowski S, Golomb G (2000) Sustained delivery and expression of DNA encapsulated in polymeric nanoparticles. Gene Ther 7:1896–1905PubMedGoogle Scholar
  112. 112.
    Chorny M, Polyak B, Alferiev IS, Walsh K, Friedman G, Levy RJ (2007) Magnetically driven plasmid DNA delivery with biodegradable polymeric nanoparticles. FASEB J 21:2510–2519PubMedGoogle Scholar
  113. 113.
    Chorny M, Fishbein I, Alferiev IS, Nyanguile O, Gaster R, Levy RJ (2006) Adenoviral gene vector tethering to nanoparticle surfaces results in receptor-independent cell entry and increased transgene expression. Mol Ther 14:382–391PubMedGoogle Scholar
  114. 114.
    Chorny M, Fishbein I, Alferiev I, Levy RJ (2009) Magnetically responsive biodegradable nanoparticles enhance adenoviral gene transfer in cultured smooth muscle and endothelial cells. Mol Pharm 6:1380–1387PubMedGoogle Scholar
  115. 115.
    Alexiou C, Jurgons R, Schmid RJ, Bergemann C, Henke J, Erhardt W, Huenges E, Parak F (2003) Magnetic drug targeting–biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment. J Drug Target 11:139–149PubMedGoogle Scholar
  116. 116.
    Weissleder R, Stark DD, Engelstad BL, Bacon BR, Compton CC, White DL, Jacobs P, Lewis J (1989) Superparamagnetic iron oxide: pharmacokinetics and toxicity. Am J Roentgenol 152:167–173Google Scholar
  117. 117.
    Grief AD, Richardson G (2005) Mathematical modelling of magnetically targeted drug delivery. J Magn Magn Mater 293:455–463Google Scholar
  118. 118.
    Dobson J (2006) Magnetic nanoparticles for drug delivery. Drug Dev Res 67:55–60Google Scholar
  119. 119.
    Polyak B, Fishbein I, Chorny M, Alferiev I, Williams D, Yellen B, Friedman G, Levy RJ (2008) High field gradient targeting of magnetic nanoparticle-loaded endothelial cells to the surfaces of steel stents. Proc Natl Acad Sci USA 105:698–703PubMedGoogle Scholar
  120. 120.
    Yellen BB, Forbes ZG, Halverson DS, Fridman G, Barbee KA, Chorny M, Levy R, Friedman G (2005) Targeted drug delivery to magnetic implants for therapeutic applications. J Magn Magn Mater 293:647–654Google Scholar
  121. 121.
    Hiramoto JS, Reilly LM, Schneider DB, Skorobogaty H, Rapp J, Chuter TA (2007) The effect of magnetic resonance imaging on stainless-steel Z-stent-based abdominal aortic prosthesis. J Vasc Surg 45:472–474PubMedGoogle Scholar
  122. 122.
    Gupta AK, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26:3995–4021PubMedGoogle Scholar
  123. 123.
    Allémann E, Gurny R, Leroux JC (1998) Biodegradable nanoparticles of poly(lactic acid) and poly(lactic-co-glycolic acid) for parenteral administration. In: Lieberman HA, Rieger MM, Banker GS (eds) Pharmaceutical dosage forms: disperse systems. Marcel Dekker, New York, pp 163–193Google Scholar
  124. 124.
    Quintanar-Guerrero D, Allemann E, Fessi H, Doelker E (1998) Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Dev Ind Pharm 24:1113–1128PubMedGoogle Scholar
  125. 125.
    Liggins RT, Hunter WL, Burt HM (1997) Solid-state characterization of paclitaxel. J Pharm Sci 86:1458–1463PubMedGoogle Scholar
  126. 126.
    Chorny M, Fishbein I, Danenberg HD, Golomb G (2002) Study of the drug release mechanism from tyrphostin AG-1295-loaded nanospheres by in situ and external sink methods. J Control Release 83:401–414PubMedGoogle Scholar
  127. 127.
    Washington C (1990) Drug release from microdisperse systems: a critical review. Int J Pharm 58:1–12Google Scholar
  128. 128.
    Vassileva V, Grant J, De Souza R, Allen C, Piquette-Miller M (2007) Novel biocompatible intraperitoneal drug delivery system increases tolerability and therapeutic efficacy of paclitaxel in a human ovarian cancer xenograft model. Cancer Chemother Pharmacol 60:907–914PubMedGoogle Scholar
  129. 129.
    Williams PD, Ranjzad P, Kakar SJ, Kingston PA (2010) Development of viral vectors for use in cardiovascular gene therapy. Viruses 2:334–371PubMedGoogle Scholar
  130. 130.
    Misra P, Reddy PC, Shukla D, Caldito GC, Yerra L, Aw TY (2008) In-stent stenosis: potential role of increased oxidative stress and glutathione-linked detoxification mechanisms. Angiology 59:469–474PubMedGoogle Scholar
  131. 131.
    Simone E, Dziubla T, Shuvaev V, Muzykantov VR (2010) Synthesis and characterization of polymer nanocarriers for the targeted delivery of therapeutic enzymes. Methods Mol Biol 610:145–164PubMedGoogle Scholar
  132. 132.
    Chorny M, Hood E, Levy RJ, Muzykantov VR (2010) Endothelial delivery of antioxidant enzymes loaded into non-polymeric magnetic nanoparticles. J Control Release 146:144–151PubMedGoogle Scholar

Copyright information

© Springer US 2012

Authors and Affiliations

  • Ilia Fishbein
    • 1
  • Michael Chorny
    • 1
  • Ivan S. Alferiev
    • 1
  • Robert J. Levy
    • 1
  1. 1.Abramson Research CenterThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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