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Merhof, Dorit

Biomedical Engineering / Biomedizinische Technik

Joint Journal of the German Society for Biomedical Engineering in VDE and the Austrian and Swiss Societies for Biomedical Engineering and the German Society of Biomaterials

Editor-in-Chief: Dössel, Olaf

Editorial Board: Augat, Peter / Habibović, Pamela / Haueisen, Jens / Jahnen-Dechent, Wilhelm / Jockenhoevel, Stefan / Knaup-Gregori, Petra / Leonhardt, Steffen / Plank, Gernot / Radermacher, Klaus M. / Schkommodau, Erik / Stieglitz, Thomas / Boenick, Ulrich / Jaramaz, Branislav / Kraft, Marc / Lenarz, Thomas / Lenthe, Harry / Lo, Benny / Mainardi, Luca / Micera, Silvestro / Penzel, Thomas / Robitzki, Andrea A. / Schaeffter, Tobias / Snedeker, Jess G. / Sörnmo, Leif / Sugano, Nobuhiko / Werner, Jürgen /

IMPACT FACTOR 2018: 1.007
5-year IMPACT FACTOR: 1.390

CiteScore 2018: 1.24

SCImago Journal Rank (SJR) 2018: 0.282
Source Normalized Impact per Paper (SNIP) 2018: 0.831

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Volume 58, Issue 5


Volume 57 (2012)

Implant-associated local drug delivery systems based on biodegradable polymers: customized designs for different medical applications

Katrin Sternberg / Svea Petersen / Niels Grabow / Volkmar Senz / Henriette Meyer zu Schwabedissen / Heyo K. Kroemer / Klaus-Peter Schmitz
Published Online: 2013-06-12 | DOI: https://doi.org/10.1515/bmt-2012-0049


Implants providing controlled, local release of active substances are of interest in different medical applications. Therefore, the focus of the present article is the development of implant-associated diffusion- or chemically controlled local drug delivery (LDD) systems based on biodegradable polymeric drug carriers. In this context, we provide new data and review our own recently published data concerning the drug release behavior of diffusion-controlled LDD systems in relation to the kind of polymer, drug content, coating mass/thickness, and layer composition. We demonstrate that polymers allow a wide range of control over the drug release characteristics. In this regard, we show that the glass transition temperature of a polymer has an impact on its drug release. Additionally, the blending of hydrophobic, semicrystalline polymers with amorphous polymers leads to an increase in the rate of drug release compared with the pure semicrystalline polymer. Moreover, the percentage loading of the embedded drug has a considerable effect on the rate and duration of drug release. Furthermore, we discuss chemically controlled LDD systems designed for the release of biomolecules, such as growth factors, as well as nanoparticle-mediated LDD systems. With our own published data on drug-eluting stents, microstents, and cochlear implants, we highlight exemplary implant-associated LDD systems designed to improve implant performance through the reduction of undesirable effects such as in-stent restenosis and fibrosis.

Keywords: biodegradable polymers; implant coating; local drug delivery; surface functionalization


  • [1]

    Acharya G, Park K. Mechanisms of controlled drug release from drug-eluting stents. Adv Drug Deliv Rev 2006; 58: 387–401.PubMedCrossrefGoogle Scholar

  • [2]

    Alexis F. Factors affecting the degradation and drug-release mechanism of poly(lactic acid) and poly[(lactic acid)-co-(glycolic acid)]. Polym Int 2005; 54: 36–46.CrossrefGoogle Scholar

  • [3]

    Andreopoulos AG. Plasticization of biodegradable polymers for use in controlled release. Clin Mater 1994; 15: 89–92.CrossrefPubMedGoogle Scholar

  • [4]

    Banai S, Chorny M, Gertz SD, et al. Locally delivered nanoencapsulated Tyrphostin (AGL-2043) reduces neointima formation in balloon-injured rat carotid and stented porcine coronary arteries. Biomaterials 2005; 26: 451–461.Google Scholar

  • [5]

    Bangham AD. Liposomes: the Babraham connection. Chem Phys Lipids 1993; 64: 275–285.PubMedCrossrefGoogle Scholar

  • [6]

    Bhargava B, Reddy NK, Karthikeyan G, et al. A novel paclitaxel-eluting porous carbon-carbon nanoparticle coated, nonpolymeric cobalt-chromium stent: evaluation in a porcine model. Catheter Cardiovasc Interv 2006; 67: 698–702.CrossrefGoogle Scholar

  • [7]

    Bohl A, Rohm HW, Ceschi P, et al. Development of a specially tailored local drug delivery system for the prevention of fibrosis after insertion of cochlear implants into the inner ear. J Mater Sci Mater Med 2012; 23: 2151–2162.PubMedCrossrefGoogle Scholar

  • [8]

    Bünger CM, Grabow N, Kröger C, et al. Iliac anastomotic stenting with a sirolimus-eluting biodegradable poly-L-lactide stent: a preliminary study after 6 weeks. J Endovasc Ther 2006; 13: 630–639.Google Scholar

  • [9]

    Bünger CM, Grabow N, Sternberg K, et al. Sirolimus-eluting biodegradable poly-L-lactide stent for peripheral vascular application: a preliminary study in porcine carotid arteries. J Surg Res 2007; 139: 77–82.Google Scholar

  • [10]

    Cen D, Gonzalez RI, Buckmeier JA, Kahlon RS, Tohidian NB, Meyskens FL Jr. Disulfiram induces apoptosis in human melanoma cells: a redox-related process. Mol Cancer Ther 2002; 1: 197–204.Google Scholar

  • [11]

    Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med 1994; 331: 496–501.Google Scholar

  • [12]

    Freier T, Kunze C, Nischan C, et al. In vitro and in vivo degradation studies for development of a biodegradable patch based on poly(3-hydroxybutyrate). Biomaterials 2002; 23: 2649–2657.Google Scholar

  • [13]

    Garg S, Serruys PW. Coronary stents: current status. J Am Coll Cardiol 2010; 56: S1–S42.CrossrefGoogle Scholar

  • [14]

    Garg S, Serruys PW. Coronary stents: looking forward. J Am Coll Cardiol 2010; 56: S43–S78.PubMedGoogle Scholar

  • [15]

    Goddard JM, Hotchkiss JH. Polymer surface modification for the attachment of bioactive compounds. Prog Polym Sci 2007; 32: 698–725.CrossrefGoogle Scholar

  • [16]

    Grabow N, Martin DP, Schmitz K-P, Sternberg K. Absorbable polymer stent technologies for vascular regeneration. J Chem Technol Biotechnol 2010; 85: 744–751.Google Scholar

  • [17]

    Grabow N, Schlun M, Sternberg K, Hakansson N, Kramer S, Schmitz K-P. Mechanical properties of laser cut poly(L-lactide) micro-specimens: implications for stent design, manufacture, and sterilization. J Biomech Eng 2005; 127: 25–31.CrossrefPubMedGoogle Scholar

  • [18]

    Grüntzig AR, Senning A, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med 1979; 301: 61–68.Google Scholar

  • [19]

    Gümüşderelioglu M, Deniz G. Sustained release of mitomycin-C from poly(DL-lactide)/poly(DL-lactide-co-glycolide) films. J Biomater Sci Polym Ed 2000; 11: 1039–1050.CrossrefGoogle Scholar

  • [20]

    Hargunani CA, Kempton JB, DeGagne JM, Trune DR. Intratympanic injection of dexamethasone: time course of inner ear distribution and conversion to its active form. Otol Neurotol 2006; 27: 564–569.CrossrefPubMedGoogle Scholar

  • [21]

    Hawkins MJ, Soon-Shiong P, Desai N. Protein nanoparticles as drug carriers in clinical medicine. Adv Drug Deliv Rev 2008; 60: 876–885.PubMedCrossrefGoogle Scholar

  • [22]

    Jedlinski Z, Kowalczuk M, Glowkowski W, Grobelny J, Szwarc M. Novel polymerization of b-butyrolactone initiated by potassium naphthalenide in the presence of a crown ether or a cryptand. Macromolecules 1991; 24: 349–352.CrossrefGoogle Scholar

  • [23]

    Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006; 48: 193–202.PubMedCrossrefGoogle Scholar

  • [24]

    Kim SH, Jeong JH, Chun KW, Park TG. Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate. Langmuir 2005; 21: 8852–8857.CrossrefPubMedGoogle Scholar

  • [25]

    Kirtane AJ, Gupta A, Iyengar S, et al. Safety and efficacy of drug-eluting and bare metal stents: comprehensive meta-analysis of randomized trials and observational studies. Circulation 2009; 119: 3198–3206.CrossrefPubMedGoogle Scholar

  • [26]

    Kober T, König I, Weber M, Kojda G. Diethyldithiocarbamate inhibits the catalytic activity of xanthine oxidase. FEBS Lett 2003; 551: 99–103.Google Scholar

  • [27]

    Lanzer P, Sternberg K, Schmitz KP, Kolodgie F, Nakazawa G, Virmani R. Drug-eluting coronary stent very late thrombosis revisited. Herz 2008; 33: 334–342.PubMedCrossrefGoogle Scholar

  • [28]

    Lendlein A. Polymere als Implantatwerkstoffe. Chem Unserer Zeit 1999; 33: 279–295.CrossrefGoogle Scholar

  • [29]

    Lipsky JJ, Shen ML, Naylor S. Overview – in vitro inhibition of aldehyde dehydrogenase by disulfiram and metabolites. Chem Biol Interact 2001; 130–132: 81–91.Google Scholar

  • [30]

    Löbler M, Sternberg K, Stachs O, et al. Polymers and drugs suitable for the development of a drug delivery drainage system in glaucoma surgery. J Biomed Mater Res B Appl Biomater 2011; 97: 388–395.CrossrefPubMedGoogle Scholar

  • [31]

    Luderer F, Begerow I, Schmidt W, et al Enhanced visualization of biodegradable polymeric vascular scaffolds by incorporation of gold, silver and magnetite nanoparticles. J Biomater Appl 2012 [Epub ahead of print].Google Scholar

  • [32]

    Luderer F, Löbler M, Rohm HW, et al. Biodegradable sirolimus-loaded poly(lactide) nanoparticles as drug delivery system for the prevention of in-stent restenosis in coronary stent application. J Biomater Appl 2011; 25: 851–875.PubMedCrossrefGoogle Scholar

  • [33]

    Marks AR. Cellular functions of immunophilins. Physiol Rev 1996; 76: 631–649.PubMedGoogle Scholar

  • [34]

    Martin DP, Williams SF. Medical applications of poly-4-hydroxybutyrate: a strong flexible absorbable biomaterial. Biochem Eng J 2003; 16: 97–105.CrossrefGoogle Scholar

  • [35]

    Marx SO, Jayaraman T, Go LO, Marks AR. Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res 1995; 76: 412–417.PubMedCrossrefGoogle Scholar

  • [36]

    Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 1986; 46: 6387–6392.PubMedGoogle Scholar

  • [37]

    Meiser BM, Morris RE, Billingham ME. Effects of cyclosporin, FK506, and rapamycin on graft-vessel disease. Lancet 1991; 338: 1297–1298.Google Scholar

  • [38]

    Minelli C, Lowe SB, Stevens MM. Engineering nanocomposite materials for cancer therapy. Small 2010; 6: 2336–2357.PubMedCrossrefGoogle Scholar

  • [39]

    Miyata T, Asami N, Uragami T. A reversibly antigen-responsive hydrogel. Nature 1999; 399: 766–769.Google Scholar

  • [40]

    Miyata T, Asami N, Uragami T. Structural design of stimuli-responsive bioconjugated hydrogels that respond to a target antigen. J Polym Sci B Polymer Phys 2009; 47: 2144–2157.CrossrefGoogle Scholar

  • [41]

    Moellering D, McAndrew J, Jo H, Darley-Usmar VM. Effects of pyrrolidine dithiocarbamate on endothelial cells: protection against oxidative stress. Free Radic Biol Med 1999; 26: 1138–1145.Google Scholar

  • [42]

    Mohacsi PJ, Tüller D, Hulliger B, Wijngaard PL. Different inhibitory effects of immunosuppressive drugs on human and rat aortic smooth muscle and endothelial cell proliferation stimulated by platelet-derived growth factor or endothelial cell growth factor. J Heart Lung Transplant 1997; 16: 484–492.Google Scholar

  • [43]

    Moon JI, Kim YS, Kim MS, et al. Effect of cyclosporine, mycophenolic acid, and rapamycin on the proliferation of rat aortic vascular smooth muscle cells: in vitro study. Transplant Proc 2000; 32: 2026–2027.CrossrefPubMedGoogle Scholar

  • [44]

    Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346: 1773–1780.Google Scholar

  • [45]

    Nebeker JR, Virmani R, Bennett CL, et al. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. J Am Coll Cardiol 2006; 47: 175–181.CrossrefPubMedGoogle Scholar

  • [46]

    Poon M, Marx SO, Gallo R, Badimon JJ, Taubman MB, Marks AR. Rapamycin inhibits vascular smooth muscle cell migration. J Clin Invest 1996; 98: 2277–2283.PubMedCrossrefGoogle Scholar

  • [47]

    Regar E, Sianos G, Serruys PW. Stent development and local drug delivery. Br Med Bull 2001; 59: 227–248.CrossrefPubMedGoogle Scholar

  • [48]

    Schultz D, Skamarauskas JT, Law N, Mitchinson MJ, Hunt JV. The inhibition of foam cell formation by sodium diethyldithiocarbamate. Free Radic Res 1995; 23: 259–271.Google Scholar

  • [49]

    Serruys PW, De Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med 1994; 331: 489–495.Google Scholar

  • [50]

    Shian S-G, Kao Y-R, Wu FY-H, Wu C-W. Inhibition of invasion and angiogenesis by zinc-chelating agent disulfiram. Mol Pharmacol 2003; 64: 1076–1084.CrossrefPubMedGoogle Scholar

  • [51]

    Sternberg K, Kramer S, Nischan C, et al. 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 2007; 18: 1423–1432.PubMedCrossrefGoogle Scholar

  • [52]

    Sternberg K, Petersen S, Grabow N, et al. Implant-associated local drug delivery systems for different medical applications. Biomed Tech (Berl) 2012; 57(Suppl. 1): 393–396.Google Scholar

  • [53]

    Stoltenberg RL, Geraghty J, Steele DM, Kennedy E, Hullett DA, Sollinger HW. Inhibition of intimal hyperplasia in rat aortic allografts with cyclosporine. Transplantation 1995; 60: 993–998.PubMedGoogle Scholar

  • [54]

    Taylor RD, Maners AW, Salari H, Baker M, Walker EM Jr. Disulfiram as a radiation modifier. Ann Clin Lab Sci 1986; 16: 443–449.Google Scholar

  • [55]

    Van de Water TR, Dinh CT, Vivero R, et al. Mechanisms of hearing loss from trauma and inflammation: otoprotective therapies from the laboratory to the clinic. Acta Otolaryngol 2010; 130: 308–311.Google Scholar

  • [56]

    Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med 2012; 63: 185–198.PubMedCrossrefGoogle Scholar

  • [57]

    Wang W, McLeod HL, Cassidy J. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int J Cancer 2003; 104: 504–511.PubMedGoogle Scholar

  • [58]

    Wulf K, Teske M, Löbler M, Luderer F, Schmitz K-P, Sternberg K. Surface functionalization of poly(ε-caprolactone) improves its biocompatibility as scaffold material for bioartificial vessel prostheses. J Biomed Mater Res B Appl Biomater 2011; 98B: 89–100.CrossrefPubMedGoogle Scholar

  • [59]

    Yilmaz B, Cetin M, Palabiyik SS, Asci A. HPLC method for determination of disulfiram in pharmaceutical preparations. Alfa Univ Int J Chem 2010; 1: 79–86.Google Scholar

About the article

Corresponding author: Prof. Dr. Katrin Sternberg, Institute for Biomedical Engineering, University of Rostock, Friedrich-Barnewitz-Straße 4, 18119 Rostock, Germany, E-mail:

Received: 2012-12-14

Accepted: 2013-05-17

Published Online: 2013-06-12

Published in Print: 2013-10-01

Citation Information: Biomedizinische Technik/Biomedical Engineering, Volume 58, Issue 5, Pages 417–427, ISSN (Online) 1862-278X, ISSN (Print) 0013-5585, DOI: https://doi.org/10.1515/bmt-2012-0049.

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