Nanotechnology Applications in Local Arterial Drug Delivery

  • Dipti Deshpande
  • Aziza Jamal-Allial
  • Kinjal Sankhe
  • Mansoor Amiji
Part of the Advances in Delivery Science and Technology book series (ADST)


Disorders of the cardiovascular system are identified as the primary cause of fatal conditions, such as atherosclerosis, myocardial infarction, and stroke. It is mainly the damage of the arterial vascular system that leads to the development of many of these fatal diseases. Abnormalities in the arterial system directly affects blood circulation and ultimately results in irreversible peripheral organ or tissue damage. This review describes the challenges and opportunities in systemic and local drug delivery to the arterial tissue. Based on the unique anatomical and physiological constraints, advances in systemic (e.g., targeted nanotechnology-based formulations) and local (e.g., drug-eluting stent implantation) delivery technologies have provided insights into arterial therapeutic approaches, especially in coronary restenosis. Significant opportunities exist in further development of multifunctional nanosystems that can be incorporated with localized delivery strategies, such as double-balloon catheters, to improve drug residence and intracellular availability.


Arterial Disease Metallic Stents Neointimal Hyperplasia Local Drug Delivery Drug Retention 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Gupta AS (2011) Nanomedicine approaches in vascular disease: a review. Nanomed Nanotechnol Biol Med 7:763–779Google Scholar
  2. 2.
    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 31:199–205PubMedCentralPubMedGoogle Scholar
  3. 3.
    Sharma S, Christopoulos C, Kukreja N, Gorog DA (2011) Local drug delivery for percutaneous coronary intervention. Pharmacol Ther 129:260–266PubMedGoogle Scholar
  4. 4.
    Wagner V, Dullaart A, Bock AK, Zweck A (2006) The emerging nanomedicine landscape. Nat Biotechnol 24:1211–1217PubMedGoogle Scholar
  5. 5.
    Lobatto ME, Fuster V, Fayad ZA, Mulder WJ (2011) Perspectives and opportunities for nanomedicine in the management of atherosclerosis. Nat Rev Drug Discov 10:835–852PubMedCentralPubMedGoogle Scholar
  6. 6.
    Lawson ND, Weinstein BM (2002) Arteries and veins: making a difference with zebrafish. Nat Rev Genet 3:674–682PubMedGoogle Scholar
  7. 7.
    Lusis AJ (2000) Atherosclerosis. Nature 407:233–241PubMedCentralPubMedGoogle Scholar
  8. 8.
    Rubanyi GM (1993) The role of endothelium in cardiovascular homeostasis and diseases. J Cardiovasc Pharmacol 22(Suppl 4):S1–S14PubMedGoogle Scholar
  9. 9.
    Meurice T, Vallet B, Bauters C, Dupuis B, Lablanche JM, Bertrand ME (1996) Role of endothelial cells in restenosis after coronary angioplasty. Fundam Clin Pharmacol 10:234–242PubMedGoogle Scholar
  10. 10.
    Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143PubMedGoogle Scholar
  11. 11.
    Schaper W, Scholz D (2003) Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol 23:1143–1151PubMedGoogle Scholar
  12. 12.
    Natarajan P, Ray KK, Cannon CP (2010) High-density lipoprotein and coronary heart disease: current and future therapies. J Am Coll Cardiol 55:1283–1299PubMedGoogle Scholar
  13. 13.
    Sprague AH, Khalil RA (2009) Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol 78:539–552PubMedCentralPubMedGoogle Scholar
  14. 14.
    Dangas G, Kuepper F (2002) Cardiology patient page. Restenosis: repeat narrowing of a coronary artery: prevention and treatment. Circulation 105:2586–2587PubMedGoogle Scholar
  15. 15.
    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
  16. 16.
    Karthikeyan G, Bhargava B (2004) Prevention of restenosis after coronary angioplasty. Curr Opin Cardiol 19:500–509PubMedGoogle Scholar
  17. 17.
    Goldberg SL, Loussararian A, De Gregorio J, Di Mario C, Albiero R, Colombo A (2001) Predictors of diffuse and aggressive intra-stent restenosis. J Am Coll Cardiol 37:1019–1025PubMedGoogle Scholar
  18. 18.
    Costa MA, Simon DI (2005) Molecular basis of restenosis and drug-eluting stents. Circulation 111:2257–2273PubMedGoogle Scholar
  19. 19.
    van Royen N, Piek JJ, Buschmann I, Hoefer I, Voskuil M, Schaper W (2001) Stimulation of arteriogenesis; a new concept for the treatment of arterial occlusive disease. Cardiovasc Res 49:543–553PubMedGoogle Scholar
  20. 20.
    van Royen N, Piek JJ, Schaper W, Fulton WF (2009) A critical review of clinical arteriogenesis research. J Am Coll Cardiol 55:17–25PubMedGoogle Scholar
  21. 21.
    Grundmann S, Piek JJ, Pasterkamp G, Hoefer IE (2007) Arteriogenesis: basic mechanisms and therapeutic stimulation. Eur J Clin Invest 37:755–766PubMedGoogle Scholar
  22. 22.
    Fuster V, Badimon L, Badimon JJ, Chesebro JH (1992) The pathogenesis of coronary artery disease and the acute coronary syndromes. New Engl J Med 326:242–250PubMedGoogle Scholar
  23. 23.
    Sobieszczyk P, Beckman J (2006) Carotid artery disease. Circulation 114:e244–e247PubMedGoogle Scholar
  24. 24.
    Gornik HL, Beckman JA (2005) Cardiology patient page. Peripheral arterial disease. Circulation 111:e169–e172PubMedGoogle Scholar
  25. 25.
    Ouriel K (2001) Peripheral arterial disease. Lancet 358:1257–1264PubMedGoogle Scholar
  26. 26.
    Libby P, Theroux P (2005) Pathophysiology of coronary artery disease. Circulation 111:3481–3488PubMedGoogle Scholar
  27. 27.
    Deshpande DD, Janero DR, Amiji MM (2011) Therapeutic strategies for endothelial dysfunction. Expert Opin Biol Ther 11:1637–1654PubMedGoogle Scholar
  28. 28.
    Dobarro D, Gomez-Rubin MC, Sanchez-Recalde A, Moreno R, Galeote G, Jimenez-Valero S, Calvo L, López de Sa E, Lopez-Sendon JL (2009) Current pharmacological approach to restore endothelial dysfunction. Cardiovasc Hematol Agents Med Chem 7:212–222PubMedGoogle Scholar
  29. 29.
    Faxon DP (2002) Systemic drug therapy for restenosis. Circulation 106:2296–2298PubMedGoogle Scholar
  30. 30.
    Law M, Rudnicka AR (2006) Statin safety: a systematic review. Am J Cardiol 97:52C–60CPubMedGoogle Scholar
  31. 31.
    Fabian E, Varga A, Picano E, Vajo Z, Ronaszeki A, Csanady M (2004) Effect of simvastatin on endothelial function in cardiac syndrome X patients. Am J Cardiol 94:652–655PubMedGoogle Scholar
  32. 32.
    Kwak BR, Mulhaupt F, Mach F (2003) Atherosclerosis: anti-inflammatory and immunomodulatory activities of statins. Autoimmun Rev 2:332–338PubMedGoogle Scholar
  33. 33.
    Sathasivam S, Lecky B (2008) Statin induced myopathy. BMJ 337:a2286PubMedGoogle Scholar
  34. 34.
    Tomasoni L, Sitia S, Borghi C, Cicero AF, Ceconi C, Cecaro F, Morganti A, De Gennaro Colonna V, Guazzi M, Morricone L, Malavazos AE, Marino P, Cavallino C, Shoenfeld Y, Turiel M (2010) Effects of treatment strategy on endothelial function. Autoimmun Rev 9:840–844PubMedGoogle Scholar
  35. 35.
    Stewart DJ, Holtz J, Bassenge E (1987) Long-term nitroglycerin treatment: effect on direct and endothelium-mediated large coronary artery dilation in conscious dogs. Circulation 75:847–856PubMedGoogle Scholar
  36. 36.
    Lei L, Guo S-R, Chen W-L, Rong H-J, Lu F (2011) Stents as a platform for drug delivery. Expert Opin Drug Deliv 8:813–831PubMedGoogle Scholar
  37. 37.
    Herdeg C, Oberhoff M, Siegel-Axel DI, Baumbach A, Blattner A, Kuttner A, Schroder S, Karsch KR (2000) Paclitaxel: a chemotherapeutic agent for prevention of restenosis? Experimental studies in vitro and in vivo. Z Kardiol 89:390–397PubMedGoogle Scholar
  38. 38.
    Herdeg C, Oberhoff M, Baumbach A, Blattner A, Axel DI, Schroder S, Heinle H, Karsch KR (2000) Local paclitaxel delivery for the prevention of restenosis: biological effects and efficacy in vivo. J Am Coll Cardiol 35:1969–1976PubMedGoogle Scholar
  39. 39.
    Jabr-Milane L, van Vlerken L, Devalapally H, Shenoy D, Komareddy S, Bhavsar M, Amiji M (2008) Multi-functional nanocarriers for targeted delivery of drugs and genes. J Control Release 130:121–128PubMedGoogle Scholar
  40. 40.
    Waugh J, Wagstaff AJ (2004) The paclitaxel (TAXUS)-eluting stent: a review of its use in the management of de novo coronary artery lesions. Am J Cardiovasc Drugs 4:257–268PubMedGoogle Scholar
  41. 41.
    Ruef J, Storger H, Schwarz F, Haase J (2008) Comparison of a polymer-free rapamycin-eluting stent (YUKON) with a polymer-based paclitaxel-eluting stent (TAXUS) in real-world coronary artery lesions. Catheter Cardiovasc Interv 71:333–339PubMedGoogle Scholar
  42. 42.
    Grube E, Schofer J, Hauptmann KE, Nickenig G, Curzen N, Allocco DJ, Dawkins KD (2010) A novel paclitaxel-eluting stent with an ultrathin abluminal biodegradable polymer: 9-month outcomes with the JACTAX HD stent. JACC Cardiovasc Interv 3:431–438PubMedGoogle Scholar
  43. 43.
    Garg S, Serruys PW (2010) Coronary stents: looking forward. J Am Coll Cardiol 56:S43–S78PubMedGoogle Scholar
  44. 44.
    Virmani R, Farb A (1999) Pathology of in-stent restenosis. Curr Opin Lipidol 10:499–506PubMedGoogle Scholar
  45. 45.
    Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, Belardi J, Sigwart U, Colombo A, Goy JJ, van den Heuvel P, Delcan J, Morel M-a (1994) A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. New Engl J Med 331:489–495PubMedGoogle Scholar
  46. 46.
    Gertz ZM, Wilensky RL (2011) Local drug delivery for treatment of coronary and peripheral artery disease. Cardiovasc Ther 29:e54–e66PubMedGoogle Scholar
  47. 47.
    Miyauchi K, Kasai T, Yokayama T, Aihara K, Kurata T, Kajimoto K, Okazaki S, Ishiyama H, Daida H (2008) Effectiveness of statin-eluting stent on early inflammatory response and neointimal thickness in a porcine coronary model. Circ J 72:832–838PubMedGoogle Scholar
  48. 48.
    Waksman R (2009) Current state of the absorbable metallic (magnesium) stent. EuroIntervention 5(Suppl F):F94–F97PubMedGoogle Scholar
  49. 49.
    Acharya G, Park K (2006) Mechanisms of controlled drug release from drug-eluting stents. Adv Drug Deliv Rev 58:387–401PubMedGoogle Scholar
  50. 50.
    Kamath KR, Barry JJ, Miller KM (2006) The Taxus drug-eluting stent: a new paradigm in controlled drug delivery. Adv Drug Deliv Rev 58:412–436PubMedGoogle Scholar
  51. 51.
    Lee Y-K, Hyung Park J, Tae Moon H, Yun Lee D, Han Yun J, Byun Y (2007) The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer. Biomaterials 28:1523–1530PubMedGoogle Scholar
  52. 52.
    Burke SE, Kuntz RE, Schwartz LB (2006) Zotarolimus (ABT-578) eluting stents. Adv Drug Deliv Rev 58:437–446PubMedGoogle Scholar
  53. 53.
    Ding NI, Pacetti SD, Tang F-W, Gada M, Roorda W (2009) XIENCE V™ stent design and rationale. J Interv Cardiol 22:S18–S27Google Scholar
  54. 54.
    de Ribamar Costa J, Jr AA (2010) Novolimus™-eluting coronary stent system. Interv Cardiol 2:645–649Google Scholar
  55. 55.
    Udipi K, Melder RJ, Chen M, Cheng P, Hezi-Yamit A, Sullivan C, Wong J, Wilcox J (2007) The next generation endeavor resolute stent: role of the BioLinx polymer system. EuroIntervention 3:137–139PubMedGoogle Scholar
  56. 56.
    Grabow N, Martin DP, Schmitz K-P, Sternberg K (2010) Absorbable polymer stent technologies for vascular regeneration. J Chem Technol Biotechnol 85:744–751Google Scholar
  57. 57.
    Seth A (2010) Moving towards biomimicry—the development of the Novel BioMime™ sirolimus-eluting coronary stent system. Eur Cardiol 6:78–82Google Scholar
  58. 58.
    Dani S, Kukreja N, Parikh P, Joshi H, Prajapati J, Jain S, Thanvi S, Shah B, Dutta JP (2008) Biodegradable-polymer-based, sirolimus-eluting Supralimus stent: 6-month angiographic and 30-month clinical follow-up results from the series I prospective study. EuroIntervention 4:59–63PubMedGoogle Scholar
  59. 59.
    Vranckx P, Serruys PW, Gambhir S, Sousa E, Abizaid A, Lemos P, Ribeiro E, Dani SI, Dalal JJ, Mehan V, Dhar A, Dutta AL, Reddy KN, Chand R, Ray A, Symons J (2006) Biodegradable-polymer-based, paclitaxel-eluting Infinnium stent: 9-month clinical and angiographic follow-up results from the SIMPLE II prospective multi-centre registry study. EuroIntervention 2:310–317PubMedGoogle Scholar
  60. 60.
    Costa JR Jr, Abizaid A, Costa R, Feres F, Tanajura LF, Abizaid A, Mattos LA, Staico R, Siqueira D, Sousa AG, Bonan R, Sousa JE (2008) Preliminary results of the hydroxyapatite nonpolymer-based sirolimus-eluting stent for the treatment of single de novo coronary lesions a first-in-human analysis of a third-generation drug-eluting stent system. JACC Cardiovasc Interv 1:545–551PubMedGoogle Scholar
  61. 61.
    Wieneke H, Dirsch O, Sawitowski T, Gu YL, Brauer H, Dahmen U, Fischer A, Wnendt S, Erbel R (2003) Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits. Catheter Cardiovasc Interv 60:399–407PubMedGoogle Scholar
  62. 62.
    Parker T, Dave V, Falotico R (2010) Polymers for drug eluting stents. Curr Pharm Des 16:3978–3988PubMedGoogle Scholar
  63. 63.
    Zhao J, Alquier L (2012) Drug-eluting stents. In: Wright JC, Burgess DJ (eds) Long acting injections and implants. Springer, New York, NY, pp 383–407Google Scholar
  64. 64.
    Kataoka T, Grube E, Honda Y, Morino Y, Hur SH, Bonneau HN, Colombo A, Di Mario C, Guagliumi G, Hauptmann KE, Pitney MR, Lansky AJ, Stertzer SH, Yock PG, Fitzgerald PJ (2002) 7-hexanoyltaxol-eluting stent for prevention of neointimal growth: an intravascular ultrasound analysis from the study to COmpare REstenosis rate between QueST and QuaDS-QP2 (SCORE). Circulation 106:1788–1793PubMedGoogle Scholar
  65. 65.
    Serruys PW, Ormiston JA, Sianos G, Sousa JE, Grube E, den Heijer P, de Feyter P, Buszman P, Schomig A, Marco J, Polonski L, Thuesen L, Zeiher AM, Bett JH, Suttorp MJ, Glogar HD, Pitney M, Wilkins GT, Whitbourn R, Veldhof S, Miquel K, Johnson R, Coleman L, Virmani R, ACTION investigators (2004) Actinomycin-eluting stent for coronary revascularization: a randomized feasibility and safety study: the ACTION trial. J Am Coll Cardiol 44:1363–1367PubMedGoogle Scholar
  66. 66.
    Kwok OH, Chow WH, Law TC, Chiu A, Ng W, Lam WF, Hong MK, Popma JJ (2005) First human experience with angiopeptin-eluting stent: a quantitative coronary angiography and three-dimensional intravascular ultrasound study. Catheter Cardiovasc Interv 66:541–546PubMedGoogle Scholar
  67. 67.
    Huang Y, Salu K, Liu X, Li S, Wang L, Verbeken E, Bosmans J, De Scheerder I (2004) Methotrexate loaded SAE coated coronary stents reduce neointimal hyperplasia in a porcine coronary model. Heart 90:195–199PubMedGoogle Scholar
  68. 68.
    Shand JA, Menown IBA (2010) Drug-eluting stents: the next generation. Interv Cardiol 2:341–350Google Scholar
  69. 69.
    Grube E, Buellesfeld L (2006) BioMatrix Biolimus A9-eluting coronary stent: a next-generation drug-eluting stent for coronary artery disease. Expert Rev Med Devices 3:731–741PubMedGoogle Scholar
  70. 70.
    Tada N, Virmani R, Grant G, Bartlett L, Black A, Clavijo C, Christians U, Betts R, Savage D, Su SH, Shulze J, Kar S (2010) Polymer-free biolimus a9-coated stent demonstrates more sustained intimal inhibition, improved healing, and reduced inflammation compared with a polymer-coated sirolimus-eluting cypher stent in a porcine model. Circ Cardiovasc Interv 3:174–183PubMedGoogle Scholar
  71. 71.
    Nakazawa G, Finn AV, John MC, Kolodgie FD, Virmani R (2007) The significance of preclinical evaluation of sirolimus-, paclitaxel-, and zotarolimus-eluting stents. Am J Cardiol 100:36M–44MPubMedGoogle Scholar
  72. 72.
    Konig A, Leibig M, Rieber J, Schiele TM, Theisen K, Siebert U, Gothe RM, Klauss V (2007) Randomized comparison of dexamethasone-eluting stents with bare metal stent implantation in patients with acute coronary syndrome: serial angiographic and sonographic analysis. Am Heart J 153:979.e1–979.e8Google Scholar
  73. 73.
    Sarisozen C, Arica B, Hincal AA, Calis S (2009) Development of biodegradable drug releasing polymeric cardiovascular stents and in vitro evaluation. J Microencapsul 26:501–512PubMedGoogle Scholar
  74. 74.
    Sternberg K, Kramer S, Nischan C, Grabow N, Langer T, Hennighausen G, Schmitz KP (2007) In vitro study of drug-eluting stent coatings based on poly(L-lactide) incorporating cyclosporine A—drug release, polymer degradation and mechanical integrity. J Mater Sci Mater Med 18:1423–1432PubMedGoogle Scholar
  75. 75.
    Deuse T, Erben RG, Ikeno F, Behnisch B, Boeger R, Connolly AJ, Reichenspurner H, Bergow C, Pelletier MP, Robbins RC, Schrepfer S (2008) Introducing the first polymer-free leflunomide eluting stent. Atherosclerosis 200:126–134PubMedGoogle Scholar
  76. 76.
    den Dekker WK, Houtgraaf JH, Onuma Y, Benit E, de Winter RJ, Wijns W, Grisold M, Verheye S, Silber S, Teiger E, Rowland SM, Ligtenberg E, Hill J, Wiemer M, den Heijer P, Rensing BJ, Channon KM, Serruys PWJC, Duckers HJ (2011) Final results of the HEALING IIB trial to evaluate a bio-engineered CD34 antibody coated stent (Genous™Stent) designed to promote vascular healing by capture of circulating endothelial progenitor cells in CAD patients. Atherosclerosis 219:245–252Google Scholar
  77. 77.
    Pendyala L, Yin X, Li J, Shinke T, Xu Y, Chen JP, King SB III, Colley K, Goodchild T, Chronos N, Hou D (2010) Polymer-free cerivastatin-eluting stent shows superior neointimal inhibition with preserved vasomotor function compared to polymer-based paclitaxel-eluting stent in rabbit iliac arteries. EuroIntervention 6:126–133PubMedGoogle Scholar
  78. 78.
    Scheller B, Schmitt A, Bohm M, Nickenig G (2003) Atorvastatin stent coating does not reduce neointimal proliferation after coronary stenting. Z Kardiol 92:1025–1028PubMedGoogle Scholar
  79. 79.
    Hong YJ, Jeong MH, Lee SR, Hong SN, Kim KH, Park HW, Kim JH, Kim W, Ahn Y, Cho JG, Park JC, Kang JC (2007) Anti-inflammatory effect of abciximab-coated stent in a porcine coronary restenosis model. J Korean Med Sci 22:802–809PubMedCentralPubMedGoogle Scholar
  80. 80.
    New G, Moses JW, Roubin GS, Leon MB, Colombo A, Iyer SS, Tio FO, Mehran R, Kipshidze N (2002) Estrogen-eluting, phosphorylcholine-coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model. Catheter Cardiovasc Interv 57:266–271PubMedGoogle Scholar
  81. 81.
    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
  82. 82.
    Regar E, Sianos G, Serruys PW (2001) Stent development and local drug delivery. Br Med Bull 59:227–248PubMedGoogle Scholar
  83. 83.
    Kandzari DE, Leon MB, Popma JJ, Fitzgerald PJ, O’Shaughnessy C, Ball MW, Turco M, Applegate RJ, Gurbel PA, Midei MG, Badre SS, Mauri L, Thompson KP, LeNarz LA, Kuntz RE, Investigators EI (2006) Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial. J Am Coll Cardiol 48:2440–2447PubMedGoogle Scholar
  84. 84.
    Brieger D, Topol E (1997) Local drug delivery systems and prevention of restenosis. Cardiovasc Res 35:405–413PubMedGoogle Scholar
  85. 85.
    Zilberman M, Eberhart RC (2006) Drug-eluting bioresorbable stents for various applications. Ann Rev Biomed Eng 8:153–180Google Scholar
  86. 86.
    Ormiston JA, Webster MW, Armstrong G (2007) First-in-human implantation of a fully bioabsorbable drug-eluting stent: the BVS poly-L-lactic acid everolimus-eluting coronary stent. Catheter Cardiovasc Interv 69:128–131PubMedGoogle Scholar
  87. 87.
    Ormiston JA, Serruys PWS (2009) Bioabsorbable coronary stents. Circ Cardiovasc Interv 2:255–260PubMedGoogle Scholar
  88. 88.
    Vogt F, Stein A, Rettemeier G, Krott N, Hoffmann R, Vom Dahl J, Bosserhoff AK, Michaeli W, Hanrath P, Weber C, Blindt R (2004) Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent. Eur Heart J 25:1330–1340PubMedGoogle Scholar
  89. 89.
    Wang X, Venkatraman SS, Boey FY, Loo JS, Tan LP (2006) Controlled release of sirolimus from a multilayered PLGA stent matrix. Biomaterials 27:5588–5595PubMedGoogle Scholar
  90. 90.
    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
  91. 91.
    Wang F, Wang J, Zhai Y, Li G, Li D, Dong S (2008) Layer-by-layer assembly of biologically inert inorganic ions/DNA multilayer films for tunable DNA release by chelation. J Control Release 132:65–73PubMedGoogle Scholar
  92. 92.
    Sun X, Zhang N (2010) Cationic polymer optimization for efficient gene delivery. Mini Rev Med Chem 10:108–125PubMedGoogle Scholar
  93. 93.
    Srinivasan R, Marchant RE, Gupta AS (2010) In vitro and in vivo platelet targeting by cyclic RGD-modified liposomes. J Biomed Mater Res A 93:1004–1015PubMedCentralPubMedGoogle Scholar
  94. 94.
    Peters D, Kastantin M, Kotamraju VR, Karmali PP, Gujraty K, Tirrell M, Ruoslahti E (2009) Targeting atherosclerosis by using modular, multifunctional micelles. Proc Natl Acad Sci U S A 106:9815–9819PubMedCentralPubMedGoogle Scholar
  95. 95.
    Li JM, Newburger PE, Gounis MJ, Dargon P, Zhang X, Messina LM (2010) Local arterial nanoparticle delivery of siRNA for NOX2 knockdown to prevent restenosis in an atherosclerotic rat model. Gene Ther 17:1279–1287PubMedCentralPubMedGoogle Scholar
  96. 96.
    Li JM, Zhang X, Nelson PR, Odgren PR, Nelson JD, Vasiliu C, Park J, Morris M, Lian J, Cutler BS, Newburger PE (2007) Temporal evolution of gene expression in rat carotid artery following balloon angioplasty. J Cell Biochem 101:399–410PubMedGoogle Scholar
  97. 97.
    Vendrov AE, Hakim ZS, Madamanchi NR, Rojas M, Madamanchi C, Runge MS (2007) Atherosclerosis is attenuated by limiting superoxide generation in both macrophages and vessel wall cells. Arterioscler Thromb Vasc Biol 27:2714–2721PubMedGoogle Scholar
  98. 98.
    Brito LA, Chandrasekhar S, Little SR, Amiji MM (2010) Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis. Biomed Eng Online 9:56PubMedCentralPubMedGoogle Scholar
  99. 99.
    Mulder WJ, Cormode DP, Hak S, Lobatto ME, Silvera S, Fayad ZA (2008) Multimodality nanotracers for cardiovascular applications. Nat Clin Pract Cardiovasc Med 5(Suppl 2):S103–S111PubMedGoogle Scholar
  100. 100.
    Briley-Saebo KC, Shaw PX, Mulder WJ, Choi SH, Vucic E, Aguinaldo JG, Witztum JL, Fuster V, Tsimikas S, Fayad ZA (2008) Targeted molecular probes for imaging atherosclerotic lesions with magnetic resonance using antibodies that recognize oxidation-specific epitopes. Circulation 117:3206–3215PubMedGoogle Scholar
  101. 101.
    Unger EM, Matsunaga TO, Schumann PA, Zutshi R (2003) Microbubbles in molecular imaging and therapy. Medicamundi 47:8Google Scholar
  102. 102.
    Cavalieri F, Finelli I, Tortora M, Mozetic P, Chiessi E, Polizio F, Brismar T, Paradossi T (2008) Polymer microbubbles as diagnostic and therapeutic gas delivery device. Chem Matter 20:8Google Scholar

Copyright information

© Controlled Release Society 2014

Authors and Affiliations

  • Dipti Deshpande
    • 1
  • Aziza Jamal-Allial
    • 1
  • Kinjal Sankhe
    • 1
  • Mansoor Amiji
    • 2
  1. 1.Department of Pharmaceutical SciencesSchool of Pharmacy, Northeastern UniversityBostonUSA
  2. 2.Department of Pharmaceutical SciencesSchool of Pharmacy, Northeastern UniversityBostonUSA

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