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Drug-Eluting Vascular Grafts

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Focal Controlled Drug Delivery

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Coronary artery bypass grafting is often associated with complications of restenosis, thrombosis, and/or infection, which may lead to graft failure and severe mortality. To prevent these complications, various commercially available drugs have been successfully incorporated into and released from vascular grafts for local treatment, thus avoiding of systemic side effects. Major trends in the development of drug-eluting vascular graft are described, such as fabrication, technological aspects, and pharmacokinetics. In reviewing the current scope and future directions of drug-eluting vascular grafts, this chapter focuses primarily on electrospinning as a promising platform technology for creating a new generation of vascular grafts, which provide controlled focal drug release and harbor prospects for long-term safety and patency.

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References

  1. Go AS, Mozaffarian D, Roger VL et al (2013) Executive summary: heart disease and stroke statistics–2013 update: a report from the American heart association. Circulation 127(1):143–152

    Article  PubMed  Google Scholar 

  2. Han J, Farah S, Domb AJ, Lelkes PI (2013) Electrospun drug-eluting fibers for vascular grafts. Pharm Res 30(7):1735–1748

    Article  CAS  PubMed  Google Scholar 

  3. Parang P, Arora R (2009) Coronary vein graft disease: pathogenesis and prevention. Can J Cardiol 25(2):e57–e62

    Article  PubMed  Google Scholar 

  4. Han J, Lazarovici P, Pomerantz C, Chen X, Wei Y, Lelkes PI (2011) Co-electrospun blends of PLGA, gelatin, and elastin as potential nonthrombogenic scaffolds for vascular tissue engineering. Biomacromolecules 12:399–408

    Article  CAS  PubMed  Google Scholar 

  5. Hirsh GM, Karnovsky MJ (1991) Inhibition of vein graft intimal proliferative lesions in the rat by heparin. Am J Pathol 139:581–587

    Google Scholar 

  6. Schwarz SM, DeBlois D, O’Brien ERM (1995) The intima: soil for atherosclerosis and restenosis. Circ Res 77:445–465

    Article  Google Scholar 

  7. Yang Z, Birkenhauer P, Julmy F, Chickering D, Ranieri JP, Merkle HP, Lüscher TF, Gander B (1999) Sustained release of heparin from polymeric particles for inhibition of human vascular smooth muscle cell proliferation. J Control Release 60(2–3):269–277

    Article  CAS  PubMed  Google Scholar 

  8. Clowes AW, Karnowsk MJ (1977) Suppression by heparin of smooth muscle cell-proliferation in injured arteries. Nature 265:625–626

    Article  CAS  PubMed  Google Scholar 

  9. Porter J, Jick H (1977) Drug-related deaths among medical in-patient. JAMA 237:879

    Article  CAS  PubMed  Google Scholar 

  10. Serruys PM, Strauss BH, Beatt KJ, Bertrand ME, Puel J, Rickards AF, Meier B, Goy J-J, Vogt P, Kappenberger L, Sigwart U (1991) Angiographic follow-up of a self-expanding coronary artery stent. N Engl J Med 324:13–17

    Article  CAS  PubMed  Google Scholar 

  11. Lehmann KG, Doria RJ, Feuer JM, Hall PX, Hoang DT (1991) Paradoxical increase in restenosis rate with chronic heparin use: final results of a randomized trial. J Am Coll Cardiol 17:181A

    Article  Google Scholar 

  12. Camenzind E, Kint P-P, Mario CD, Ligthart J, Van der Giessen W, Boersma E, Serruys PW (1995) Intracoronary heparin delivery in humans: acute feasibility and long-term results. Circulation 92:2463–2472

    Article  CAS  PubMed  Google Scholar 

  13. Edelman ER, Adams DH, Karnovsky MJ (1990) Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury. Proc Natl Acad Sci U S A 87(10):3773–3777

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Edelman ER, Nathan A, Katada M, Gates J, Karnovsky MJ (2000) Perivascular graft heparin delivery using biodegradable polymer wraps. Biomaterials 21:2279–2286

    Article  CAS  PubMed  Google Scholar 

  15. Fattori R, Piva T (2003) Drug-eluting stents in vascular intervention. Lancet 361(9353):247–249

    Article  PubMed  Google Scholar 

  16. Innocente F, Mandracchia D, Pektok E, Nottelet B, Tille JC, de Valence S, Faggian G, Mazzucco A, Kalangos A, Gurny R, Moeller M, Walpoth BH (2009) Paclitaxel-eluting biodegradable synthetic vascular prostheses: a step toward reduction of neointima formation? Circulation 120(11 Suppl):S37–S45

    Article  CAS  PubMed  Google Scholar 

  17. Park DW, Hong MK, Mintz GS, Lee CW, Song JM, Han KH et al (2006) Two-year follow-up of the quantitative angiographic and volumetric intravascular ultrasound analysis after nonpolymeric paclitaxel-eluting stent implantation: late “catch-up” phenomenon from ASPECT Study. J Am Coll Cardiol 48(12):2432–2439

    Article  CAS  PubMed  Google Scholar 

  18. Loukas M, Groat C, Khangura R, Owens DG, Anderson RH (2009) The normal and abnormal anatomy of the coronary arteries. Clin Anat 22(1):114–128

    Article  PubMed  Google Scholar 

  19. http://nyp.org/health/cardiac-arteries.html, accessed Feb 2, 2013

  20. Sarkar S, Sales KM, Hamilton G, Seifalian AM (2007) Addressing thrombogenicity in vascular graft construction. J Biomed Mater Res B Appl Biomater 82(1):100–108

    Article  PubMed  Google Scholar 

  21. Orr AW, Sanders JM, Bevard M, Coleman E, Sarembock IJ, Schwartz MA (2005) The subendothelial extracellular matrix modulates NF-kappaB activation by flow: a potential role in atherosclerosis. J Cell Biol 169(1):191–202

    Article  CAS  PubMed  Google Scholar 

  22. Stephan S, Ball SG, Williamson M, Bax DV, Lomas A, Shuttleworth CA, Kielty CM (2006) Cell-matrix biology in vascular tissue engineering. J Anat 209(4):495–502

    Article  CAS  PubMed  Google Scholar 

  23. Luong-Van E, Grondahl L, Chua KN, Leong KW, Nurcombe V, Cool SM (2006) Controlled release of heparin from poly(epsilon-caprolactone) electrospun fibers. Biomaterials 27:2042–2050

    Article  CAS  PubMed  Google Scholar 

  24. Scott-Burden T, Vanhoutte PM (1994) Regulation of smooth muscle cell growth by endothelium-derived factors. Tex Heart Inst J 21(1):91–97

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Beamish JA, He B, Kottke-Marchant K, Marchant RE (2010) Molecular regulation of contractile smooth muscle cell phenotype: implications for vascular tissue engineering. Tissue Eng Part B Rev 16(5):467–491

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Tucker EI, Marzec UM, White TC, Hurst S, Rugonyi S, McCarty OJ, Gailani D, Gruber A, Hanson SR (2009) Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI. Blood 113(4):936–944

    Article  CAS  PubMed  Google Scholar 

  27. Taite LJ, Yang P, Jun HW, West JL (2008) Nitric oxide-releasing polyurethane-PEG copolymer containing the YIGSR peptide promotes endothelialization with decreased platelet adhesion. J Biomed Mater Res B Appl Biomater 84(1):108–116

    Article  PubMed  Google Scholar 

  28. Osada T, Yamamura K, Yano K, Fujimoto K, Mizuno K, Sakurai T, Nabeshima T (2000) Distribution and serum concentration of sisomicin released from fibrin glue-sealed Dacron graft in the rat and human. J Biomed Mater Res 52(1):53–57

    Article  CAS  PubMed  Google Scholar 

  29. Huh J, Chen JC, Furman GM, Malki C, King B, Kafie F, Wilson SE (1998) Local treatment of prosthetic vascular graft infection with multivesicular liposome-encapsulated amikacin. J Surg Res 74(1):54–58

    Article  CAS  PubMed  Google Scholar 

  30. Zetrenne E, McIntosh BC, McRae MH, Gusberg R, Evans GR, Narayan D (2007) Prosthetic vascular graft infection: a multi-center review of surgical management. Yale J Biol Med 80(3):113–121

    PubMed Central  PubMed  Google Scholar 

  31. O'Brien T, Collin J (1992) Prosthetic vascular graft infection. Br J Surg 79(12):1262–1267

    Article  PubMed  Google Scholar 

  32. Chandy T, Rao GH, Wilson RF, Das GS (2001) Development of poly(Lactic acid)/chitosan co-matrix microspheres: controlled release of taxol-heparin for preventing restenosis. Drug deliv 8(2):77–86

    Article  CAS  PubMed  Google Scholar 

  33. Pires NM, van der Hoeven BL, de Vries MR, Havekes LM, van Vlijmen BJ, Hennink WE, Quax PH, Jukema JW (2005) Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(epsilon-caprolactone) stent cuff. Biomaterials 26:5386–5394

    Article  CAS  PubMed  Google Scholar 

  34. Khan W, Farah S, Domb AJ (2012) Drug eluting stents: developments and current status. J Control Release 161:703–712

    Article  CAS  PubMed  Google Scholar 

  35. Lim HJ, Nam HY, Lee BH, Kim DJ, Ko JY, Park JS (2007) A novel technique for loading of paclitaxel-PLGA nanoparticles onto ePTFE vascular grafts. Biotechnol Prog 23(3):693–697

    Article  CAS  PubMed  Google Scholar 

  36. Chatterjee S, Pandey A (2008) Drug eluting stents: friend or foe? A review of cellular mechanisms behind the effects of Paclitaxel and sirolimus eluting stents. Curr Drug Metab 9(6):554–566

    Article  CAS  PubMed  Google Scholar 

  37. Nguyen KT, Shaikh N, Wawro D, Zhang S, Schwade ND, Eberhart RC, Tang L (2004) Molecular response of vascular smooth muscle cells to paclitaxel-eluting bioresorbable stent materials. J Biomed Mater Res A 69(3):513–524

    Article  PubMed  Google Scholar 

  38. Marx SO, Marks AR (2001) Bench to bedside: the development of rapamycin and its application to stent restenosis. Circulation 104(8):852–855

    Article  CAS  PubMed  Google Scholar 

  39. Matter CM, Rozenberg I, Jaschko A, Greutert H, Kurz DJ et al (2006) Effects of tacrolimus or sirolimus on proliferation of vascular smooth muscle and endothelial cells. J Cardiovasc Pharm 48(6):286–292

    Article  CAS  Google Scholar 

  40. Sanders WG, Hogrebe PC, Grainger DW, Cheung AK, Terry CM (2012) A biodegradable perivascular wrap for controlled, local and directed drug delivery. J Control Release 161(1):81–89

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Kleinedler J, Pjescic I, Bullock KK, Khaliq A, Foley JD, Dugas TR (2012) Arterial pharmacokinetics of red wine polyphenols: implications for novel endovascular therapies targeting restenosis. J Pharm Sci 101(5):1917–1931

    Article  CAS  PubMed  Google Scholar 

  42. Hedin U, Daum G, Clowes AW (1998) Heparin inhibits thrombin-induced mitogen-activated protein kinase signaling in arterial smooth muscle cells. J Vasc Surg 27:512–520

    Article  CAS  PubMed  Google Scholar 

  43. Del Gaudio C, Ercolani E, Galloni P, Santilli F, Baiguera S, Polizzi L, Bianco A (2013) Aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds: potential small-diameter vascular grafts for thrombosis prevention. J Mater Sci Mater Med 24(2):523–532

    Article  PubMed  Google Scholar 

  44. Roehrborn AA, Hansbrough JF, Gualdoni B, Kim S (1995) Lipid-based slow-release formulation of amikacin sulfate reduces foreign body-associated infections in mice. Antimicrob Agents Chemother 39:1752

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Schassan HH (1976) Antimicrobial effectiveness of sisomicin. I: in vitro activity of sisomicin compared with gentamicin, tobramycin, amikacin and kanamycin. Infection 4(2):35–41

    Article  CAS  PubMed  Google Scholar 

  46. Hisashi S, Marui A, Hirose K, Nomura K, Arai Y, Chandra S, Huang Y et al (2008) Less-invasive and highly effective method for preventing methicillin-resistant Staphylococcus aureus graft infection by local sustained release of vancomycin. J Thorac Cardiovasc Surg 135(1):25–31

    Article  Google Scholar 

  47. Morishima M, Akira M, Shigeki Y, Takamasa N, Naoki N, Suong-Hyu H, Tadashi I, Ryuzo S (2010) Sustained release of vancomycin from a new biodegradable glue to prevent methicillin-resistant Staphylococcus aureus graft infection. Interact Cardiovasc Thorac Surg 11(1):52–55

    Article  PubMed  Google Scholar 

  48. Anderson JM, Shive MS (2012) Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 64:72–82

    Article  Google Scholar 

  49. Rajathurai T, Rizvi SI, Lin H, Angelini GD, Newby AC, Murphy GJ (2010) Periadventitial Rapamycin-eluting microbeads promote vein graft disease in long-term Pig vein-into-artery interposition grafts. Circ Cardiovasc Interv 3(2):157–165

    Article  CAS  PubMed  Google Scholar 

  50. Qi XR, Yan Y, Ma XD, Li TY, Nie XY, Yang BB (2007) Development of a local vasodilator delivery system using fibrin glue to prevent arterial graft from spasm. J Biomed Mater Res A 82(1):139–144

    Article  PubMed  Google Scholar 

  51. Winternitz CI, Jackson JK, Oktaba AM, Burt HM (1996) Development of a polymeric surgical paste formulation for taxol. Pharm Res 13(3):368–375

    Article  CAS  PubMed  Google Scholar 

  52. Gander B, Wehrli E, Alder R, Merkle HP (1995) Quality improvement of spray-dried, protein-loaded D, L-PLA microspheres by appropriate polymer solvent selection. J Microencapsul 12(1):83–97

    Article  CAS  PubMed  Google Scholar 

  53. Westedt U, Kalinowski M, Wittmar M, Merdan T, Unger F, Fuchs J, Schäller 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(1):41–51

    Article  CAS  PubMed  Google Scholar 

  54. Doshi J, Reneker DH (1995) Electrospinning process and applications of electrospun fibers. J Electrostat 35:151–160

    Article  CAS  Google Scholar 

  55. Biondi M, Ungaro F, Quaglia F, Netti PA (2008) Controlled drug delivery in tissue engineering. Adv Drug Deliv Rev 60:229–242

    Article  CAS  PubMed  Google Scholar 

  56. Kowalczyk T, Nowicka A, Elbaum D, Kowalewski TA (2008) Electrospinning of bovine serum albumin. Optimization and the use for production of biosensors. Biomacromolecules 9:2087–2090

    Article  CAS  PubMed  Google Scholar 

  57. Montero RB, Vial X, Nguyen DT, Farhand S, Reardon M, Pham SM, Tsechpenakis G, Andreopoulos FM (2012) bFGF-containing electrospun gelatin scaffolds with controlled nano-architectural features for directed angiogenesis. Acta Biomater 8:1778–1791

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Ekaputra AK, Prestwich GD, Cool SM, Hutmacher DW (2011) The three-dimensional vascularization of growth factor-releasing hybrid scaffold of poly (epsilon-caprolactone)/collagen fibers and hyaluronic acid hydrogel. Biomaterials 32:8108–8117

    Article  CAS  PubMed  Google Scholar 

  59. Lelkes PI, Li M, Perets A, Lin L, Han J, Woerdeman DL (2008) Electrospinning of natural proteins for tissue engineering scaffolding. In: Reis RL (ed) Handbook of natural-based polymers for biomedical applications. Woodhead, Cambridge

    Google Scholar 

  60. Han J (2010) Co-electrospun blends of PLGA, gelatin and elastin as nonthrombogenic scaffolds for vascular tissue engineering. Dissertation, Drexel University

    Google Scholar 

  61. Barnes CP, Sell SA, Boland ED, Simpson DG, Bowlin GL (2007) Designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev 59(14):1413–1433

    Article  CAS  PubMed  Google Scholar 

  62. Kim K, Luu YK, Chang C, Fang D, Hsiao BS, Chu B, Hadjiargyrou M (2004) Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. J Control Release 98(1):47–56

    Article  CAS  PubMed  Google Scholar 

  63. Li M, Mondrinos MJ, Gandhi MR, Ko FK, Weiss AS, Lelkes PI (2005) Electrospun protein fibers as matrices for tissue engineering. Biomaterials 26(30):5999–6008

    Article  CAS  PubMed  Google Scholar 

  64. Li M, Mondrinos MJ, Chen X, Gandhi MR, Ko FK, Lelkes PI (2006) Co-electrospun poly(lactide-co-glycolide), gelatin, and elastin blends for tissue engineering scaffolds. J Biomed Mater Res A 79(4):963–973

    Article  PubMed  Google Scholar 

  65. Ji W, Sun Y, Yang F, van den Beucken JJ, Fan M, Chen Z, Jansen JA (2011) Bioactive electrospun scaffolds delivering growth factors and genes for tissue engineering applications. Pharm Res 28(6):1259–1272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Chakraborty S, Liao IC, Adler A, Leong KW (2009) Electrohydrodynamics: a facile technique to fabricate drug delivery systems. Adv Drug Deliv Rev 61(12):1043–1054

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Yoo HS, Kim TG, Park TG (2009) Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery. Adv Drug Deliv Rev 61(12):1033–1042

    Article  CAS  PubMed  Google Scholar 

  68. Chen JP, Su CH (2011) Surface modification of electrospun PLLA nanofibers by plasma treatment and cationized gelatin immobilization for cartilage tissue engineering. Acta Biomater 7(1):234–243

    Article  CAS  PubMed  Google Scholar 

  69. Lee J, Yoo JJ, Atala A, Lee SJ (2012) The effect of controlled release of PDGF-BB from heparin-conjugated electrospun PCL/gelatin scaffolds on cellular bioactivity and infiltration. Biomaterials 33(28):6709–6720

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Hyung RM II, Kim JS, Konno T, Takai M, Ishihara K (2009) Preparation of electrospun poly(L-lactide-co-caprolactone-co-glycolide)/phospholipid polymer/rapamycin blended fibers for vascular application. Curr Appl Phys 9:249–251

    Article  Google Scholar 

  71. Mo XM, Xu CY, Kotaki M, Ramakrishna S (2004) Electrospun P(LLA-CL) nanofiber: a biomimetic extracellular matrix for smooth muscle cell and endothelial cell proliferation. Biomaterials 25:1883–1890

    Article  CAS  PubMed  Google Scholar 

  72. He SW, Li SS, Hu ZM, Yu JR, Chen L, Zhu J (2011) Effects of three parameters on the diameter of electrospun poly(ethylene oxide) nanofibers. J Nanosci Nanotechnol 11:1052–1059

    Article  CAS  PubMed  Google Scholar 

  73. Tan EP, Ng SY, Lim CT (2005) Tensile testing of a single ultrafine polymeric fiber. Biomaterials 26:1453–1456

    Article  CAS  PubMed  Google Scholar 

  74. Uttayarat P, Perets A, Li M, Pimton M, Stachelek SJ, Alferiev I, Composto RJ, Levy RJ, Lelkes PI (2010) Micropatterning of three-dimensional electrospun polyurethane vascular grafts. Acta Biomater 6:4229–4237

    Article  CAS  PubMed  Google Scholar 

  75. Verreck G, Chun I, Rosenblatt J, Peeters J, Dijck AV, Mensch J, Noppe M, Brewster ME (2003) Incorporation of drugs in an amorphous state into electrospun nanofibers composed of a water-insoluble, nonbiodegradable polymer. J Control Release 92:349–360

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, School of Medicine, Emory University and Parker H. Petit Institute of Biotechnology and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA

    Jingjia Han

  2. Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA, USA

    Peter I. Lelkes

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  1. Jingjia Han
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  2. Peter I. Lelkes
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Correspondence to Peter I. Lelkes .

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Editors and Affiliations

  1. School of Pharmacy-Faculty of Medicine The Hebrew University of Jerusalem, Jerusalem, Israel

    Abraham J. Domb

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Balanagar, Hyderabad, Andhra Pradesh, India

    Wahid Khan

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Han, J., Lelkes, P.I. (2014). Drug-Eluting Vascular Grafts. In: Domb, A., Khan, W. (eds) Focal Controlled Drug Delivery. Advances in Delivery Science and Technology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-9434-8_19

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