Skip to main content
SpringerLink
Log in

The Application of Electrostatic Dry Powder Deposition Technology to Coat Drug-Eluting Stents

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

A novel methodology has been introduced to effectively coat intravascular stents with sirolimus-loaded polymeric microparticles.

Methods

Dry powders of the microparticulate formulation, consisting of non-erodible polymers, were produced by a supercritical, aerosol, solvent extraction system (ASES). A design of experiment (DOE) approach was conducted on the independent variables, such as organic/CO2 phase volume ratio, polymer weight and stirring-rate, while regression analysis was utilized to interpret the influence of all operational parameters on the dependent variable of particle size. The dry powders, so formed, entered an electric field created by corona charging and were sprayed on the earthed metal stent. Furthermore, the thermal stability of sirolimus was investigated to define the optimum conditions for fusion to the metal surfaces.

Results

The electrostatic dry powder deposition technology (EDPDT) was used on the metal strut followed by fusion to produce uniform, reproducible and accurate coatings. The coated stents exhibited sustained release profiles over 25 days, similar to commercial products. EDPDT-coated stents displayed significant reduced platelet adhesion.

Conclusions

EDPDT appeared to be a robust accurate and reproducible technology to coat eluting stents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Sigwart U, Puel J, Mirkovitch V, Joffe F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987;316:701–06.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Lally C, Kelly DJ, Prendergast PG. Stents. In: Akay M, editor. Encyclopedia of biomedical engineering. New Jersey: Willey; 2006. p. 1–10.

    Google Scholar 

  4. Hara H, Nakamura M, Palmaz JC, Schwartz RS. Role of stent and coatings on restenosis and thrombosis. Adv Drug Deliv Rev. 2006;58:37–86.

    Article  CAS  Google Scholar 

  5. Sousa JE, Serruys PW, Costa MA. New frontier in cardiology: drug eluting stents: Part II. Circulation. 2003;107:2383–89.

    Article  PubMed  Google Scholar 

  6. Lewis AL, Cumming ZL, Goreish HH, Kirkwood LC, Tolhurst LA, Stratford PW. Crosslinkable coatings from phosphorylcholine — base polymers. Biomaterials. 2001;22:99–111.

    Article  PubMed  CAS  Google Scholar 

  7. Lewis AL, Furze JD, Small S, Robertson JD, Higgins BJ, Taylor S, et al. Long-term stability of a coronary stent coating post-implantation. J Biomed Mater Res Appl B Biomater. 2002;63:699–705.

    Article  CAS  Google Scholar 

  8. De Scheerder I, Wang K, Wilczek K, Meuleman D, van Amsterdam R, Vogel G, et al. Experimental study of thrombogenicity and foreign body reaction induced by heparin-coated coronary stents. Circulation. 1997;95:1549–53.

    PubMed  Google Scholar 

  9. Serruys PW, van Hout B, Bonnier H, Legrand V, Garcia E, Macaya C, et al. Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet. 1998;352:673–81.

    Article  PubMed  CAS  Google Scholar 

  10. Whelan DM, van der Giessen WJ, Krabbendam SC, van Vliet EA, Verdouw PD, Serruys PW, et al. Biocompatibility of phosphorylcholine coated stents in normal porcine coronary arteries. Heart Drug. 2000;83:338–45.

    CAS  Google Scholar 

  11. Chen MC, Liang HF, Chiu YL, Chang Y, Wei HJ, Sung HW. A novel drug-eluting stent spray-coated with multi-layers of collagen and sirolimus. J Control Rel. 2005;108:178–89.

    Article  CAS  Google Scholar 

  12. Tarcha PJ, Verlee D, Hui HW, Setesak J, Antohe B, Radulesku D, et al. The application of Ink-Jet Technology for the coating and loading of drug-eluting stents. Ann Biomed Eng. 2007;35:1791–99.

    Article  PubMed  Google Scholar 

  13. Ozbek C, Heisel A, Gross B, Bay W, Schieffer H. Coronary implantation of silicone-carbide-coated Palmaz-Schatz stents in patients with high risk of stent thrombosis without oral anticoagulation. Cathet Cardiovasc Diagn. 1997;41:71–8.

    Article  PubMed  CAS  Google Scholar 

  14. Chen JY, Leng YX, Tian XB, Wang LP, Huang N, Chu PK, et al. Antithrombogenic investigation of surface energy and optical bandgap and hemocompatibility mechanism of Ti(Ta(+5))O2 thin films. Biomaterials. 2002;23:2545–52.

    Article  PubMed  CAS  Google Scholar 

  15. Ekqvist S, Svedman C, Lundh T, Möller H, Björk J, Bruze M. A correlation found between gold concentration in blood and patch test reactions in patients with coronary stents. Contact Dermatitis. 2008;59:137–42.

    Article  PubMed  CAS  Google Scholar 

  16. Kuraishi K, Iwata H, Nakano S, Kubota S, Tonami H, Toda M, et al. Development of nanofiber-covered stents using electrospinning: in vitro and acute phase in vivo experiments. J Biomed Mater Res B Appl Biomater. 2009;88:230–9.

    PubMed  Google Scholar 

  17. Kim TG, Lee H, Jang Y, Park TG. Controlled release of paclitaxel from heparinized metal stent fabricated by layer-by-layer assembly of polylysine and hyaluronic acid-g-poly(lactic-co-glycolic acid) micelles encapsulating paclitaxel. Biomacromolecules; 2009. (in press).

  18. De Scheerder I, Verbeken E, Van Humbeeck J. Metallic surface modification. Semin Interv Cardiol. 1998;3:139–44.

    Article  PubMed  Google Scholar 

  19. FDA patient safety news. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/printer.cfm?id=356 Importance of antiplatelet therapy with drug eluting stents. (assessed 09/03)

  20. Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation. 2004;109:701–5.

    Article  PubMed  Google Scholar 

  21. Bleich J, Mueller BW, Wassmus W. Aerosol solvent extraction system. A new microparticle production technique. Int J Pharm. 1993;97:111–21.

    Article  CAS  Google Scholar 

  22. Zochowska D, Bartłomiejczyk I, Kaminska A, Senatorski G, Paczek L. High-performance liquid chromatography versus immunoassay for the measurement of sirolimus: comparison of two methods. Transplant Proc. 2006;38:78–80.

    Article  PubMed  CAS  Google Scholar 

  23. Steckel H, Thies J, Müller BW. Micronizing of steroids for pulmonary delivery by supercritical carbon dioxide. Int J Pharma. 1997;152:99–110.

    Article  CAS  Google Scholar 

  24. Bustami RT, Chan HK, Dehghani F, Foster NR. Generation of micro - particles of proreins for aerosol delivery using high pressure modified carbon dioxide. Pharm Res. 2000;17:1360–66.

    Article  PubMed  CAS  Google Scholar 

  25. Kim YH, Sioutas C, Fine P, Shing KS. Effect of albumin on physical characteristics of drug particles produced by supercritical fluid technology. Powder Technol. 2008;182:354–63.

    Article  CAS  Google Scholar 

  26. Ghaderi R, Artursson P, Carlfors J. A new method for preparing biodegradable microparticles and entrapment of hydrocortisone in DL-PLG microparticles using supercritical fluids. Eur J Pharm Sci. 2000;10:1–9.

    Article  PubMed  CAS  Google Scholar 

  27. Nelson FC, Stachel SJ, Eng CP, Sehgal SN. Manipulation of the C(22)–C(27) region of rapamycin: stability issues and biological implications. Bioorg Med Chem Lett. 1999;9:295–300.

    Article  PubMed  CAS  Google Scholar 

  28. Ricciutelli M, Di Martino P, Barboni L, Martelli S. Evaluation of rapamycin chemical stability in volatile-organic solvents by HPLC. J Pharm Biomed Anal. 2006;41:1070–74.

    Article  PubMed  CAS  Google Scholar 

  29. Zhou CC, Stewart KD, Dhaon MK. An intramolecular ionic hydrogen bond stabilizes a cis amide bond rotamer of a ring-opened rapamycin-degradation product. Magn Reson Chem. 2005;43:41–6.

    Article  PubMed  CAS  Google Scholar 

  30. Lee YK, Park JH, Moon HT, Lee D, Yun JH, Byun Y. The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer. Biomaterials. 2007;28:1523–30.

    Article  PubMed  CAS  Google Scholar 

  31. Wang X, Venkatraman SS, Boey FY, Loo JS, Tan LP. Controlled release of sirolimus from a multilayered PLGA stent matrix. Biomaterials. 2006;27:5588–95.

    Article  PubMed  CAS  Google Scholar 

  32. Barletta M, Gisario A, Tagliaferri V. Electrostatic spray deposition (ESD) of polymeric powders on thermoplastic (PA66) substrate. Surf Coat Techn. 2006;201:296–308.

    Article  CAS  Google Scholar 

  33. Thierry B, Merhi Y, Silver J, Tabrizian M. Biodegradable membrane-covered stent from chitosanbased polymers

  34. Lewis A. Phosphorylcholine-based polymers and their use in the prevention of biofouling. Colloids Surf, B Biointerfaces. 2000;18:261–75.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Greenwich, School of Science, Medway Campus, Central Avenue, Chatham Maritime, Kent, ME4 4 TB, UK

    Ravi Kumar Nukala, Harikrishna Boyapally, Ian J. Slipper, Andy P. Mendham & Dennis Douroumis

Authors
  1. Ravi Kumar Nukala
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Harikrishna Boyapally
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ian J. Slipper
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andy P. Mendham
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dennis Douroumis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dennis Douroumis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nukala, R.K., Boyapally, H., Slipper, I.J. et al. The Application of Electrostatic Dry Powder Deposition Technology to Coat Drug-Eluting Stents. Pharm Res 27, 72–81 (2010). https://doi.org/10.1007/s11095-009-0008-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-009-0008-y

Key Words

Search

Navigation