Skip to main content

Advertisement

Log in

Controlled release of triamcinolone acetonide from polyurethane implantable devices: application for inhibition of inflammatory-angiogenesis

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

The purpose of this study was to develop triamcinolone acetonide-loaded polyurethane implants (TA PU implants) for the local treatment of different pathologies including arthritis, ocular and neuroinflammatory disorders. The TA PU implants were characterized by FTIR, SAXS and WAXS. The in vitro and in vivo release of TA from the PU implants was evaluated. The efficacy of TA PU implants in suppressing inflammatory-angiogenesis in a murine sponge model was demonstrated. FTIR results revealed no chemical interactions between polymer and drug. SAXS results indicated that the incorporation of the drug did not disturb the polymer morphology. WAXS showed that the crystalline nature of the TA was preserved after incorporation into the PU. The TA released from the PU implants efficiently inhibited the inflammatory-angiogenesis induced by sponge discs in an experimental animal model. Finally, TA PU implants could be used as local drug delivery systems because of their controlled delivery of TA.

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

Access this article

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. Ayres E. Phase morphology of hydrolysable polyurethanes derived from aqueous dispersions. Eur Polym J. 2007;43:3510–1.

    Article  CAS  Google Scholar 

  2. Da Silva GR. Biodegradation of polyurethanes and nanocomposites to non-cytotoxic degradation products. Polym Degrad Stabil. 2010;95(4):491–9.

    Article  Google Scholar 

  3. Jiang X. Synthesis and degradation of nontoxic biodegradable waterborne polyurethanes elastomer with poly(ε-caprolactone) and poly(ethylene glycol) as soft segment. Eur Polym J. 2007;43:1838–46.

    Article  CAS  Google Scholar 

  4. Zhang C. Synthesis and characterization of biocompatible, degradable, light curable, polyurethane-based elastic hydrogels. J Biomed Mater Res. 2007;82(3):637.

    Article  Google Scholar 

  5. Laschke MW. In vivo biocompatibility and vascularization of biodegradable porous polyurethane scaffolds for tissue engineering. Acta Biomater. 2009;5:1991–2001.

    Article  CAS  Google Scholar 

  6. Hausner T. Nerve regeneration using tubular scaffolds from biodegradable polyurethane. Acta Neurochir Suppl. 2007;100:69–72.

    Article  CAS  Google Scholar 

  7. Tongkui C. Rapid prototyping of a double-layer polyurethane-collagen conduit for peripheral nerve regeneration. Tissue Eng Part C Methods. 2009;15:1–9.

    Article  Google Scholar 

  8. Williamson MR. PCL-PU composite vascular scaffold production for vascular tissue engineering: Attachment, proliferation and bioactivity of human vascular endothelial cells. Biomaterials. 2009;27(19):3608–16.

    Google Scholar 

  9. Grenier S. Polyurethane biomaterials for fabricating 3D porous scaffolds and supporting vascular cells. J Biomed Mater Res, Part A. 2007;82:802–9.

    Article  Google Scholar 

  10. Zhang L. A novel small-diameter vascular graft: in vivo behavior of biodegradable three-layered tubular scaffolds. Biotechnol Bioeng. 2008;99:1007–15.

    Article  CAS  Google Scholar 

  11. Lee CR. Fibrinpolyurethane composites for articular cartilage tissue engineering: a preliminary analysis. Tissue Eng. 2005;11:1562–3.

    Article  CAS  Google Scholar 

  12. Eyrich D. In vitro and in vivo cartilage engineering using a combination of chondrocyte-seeded long-term stable fibrin gels and polycaprolactone-based polyurethane scaffolds. Tissue Eng. 2007;13:2207–8.

    Article  CAS  Google Scholar 

  13. Bonakdar S. Preparation and characterization of polyvinyl alcohol hydrogels crosslinked by biodegradable polyurethane for tissue engineering of cartilage. Mater Sci Eng, C. 2010;30(4):636–43.

    Article  CAS  Google Scholar 

  14. Gogolewski S. Regeneration of bicortical defects in the iliac crest of estrogen-deficient sheep, using new biodegradable polyurethane bone graft substitutes. J Biomed Mater Res, Part A. 2006;77:802.

    Article  Google Scholar 

  15. Bil M. Optimization of the structure of polyurethanes for bone tissue engineering applications. Acta Biomater. 2010;6(7):2501.

    Article  CAS  Google Scholar 

  16. Ryszkowska JL. Biodegradable polyurethane composite scaffolds containing Bioglass® for bone tissue engineering. Acta Biomater. 2010;6(7):2484–93.

    Article  Google Scholar 

  17. Omar S. Colon-specific drug delivery for mebeverine hydrochloride. J Drug Target. 2007;15(10):691.

    Article  CAS  Google Scholar 

  18. Smith M. Primary porcine brain microvascular endothelial cells: biochemical and functional characterisation as a model for drug transport and targeting. J Drug Target. 2007;15(4):253–8.

    Article  CAS  Google Scholar 

  19. Da Silva GR. Controlled release of dexamethasone acetate from biodegradable and biocompatible polyurethane and polyurethane nanocomposite. J Drug Target. 2009;17(5):374–83.

    Article  Google Scholar 

  20. Donelli G. Efficacy of antiadhesive, antibiotic and antiseptic coatings in preventing catheter-related infections: review. J Chemother. 2001;13:595.

    CAS  Google Scholar 

  21. Francolini I. Polyurethane anionomers containing metal ions with antimicrobial properties: thermal, mechanical and biological characterization. Acta Biomater. 2010;6:3482.

    Article  CAS  Google Scholar 

  22. Huynh TTN. Characterization of a polyurethane-based controlled release system for local delivery of chlorhexidine diacetate. Eur J Pharma Biopharm. 2010;74:255–64.

    Article  CAS  Google Scholar 

  23. Johnson T. Design of intravaginal ring for simultaneous delivery of antiretroviral drugs. Antiviral Res. 2009;82(2):A74.

    Article  Google Scholar 

  24. Johnson TJ. Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir. Eur J Pharma Biopharm. 2010;39(4):203–12.

    CAS  Google Scholar 

  25. Da Silva GR. Biodegradable polyurethane nanocomposites containing dexamethasone for ocular route. Mater Sci Eng, C. 2011;31(2):414–22.

    Article  Google Scholar 

  26. Sivak WN. LDI-glycerol polyurethane implants exhibit controlled release of DB-67 and anti-tumor activity in vitro against malignant gliomas. Acta Biomater. 2008;4:852–62.

    Article  CAS  Google Scholar 

  27. Sivak WN. Simultaneous drug release at different rates from biodegradable polyurethane foams. Acta Biomater. 2009;5(7):2398–408.

    Article  CAS  Google Scholar 

  28. Kim H. Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration. Retina. 2006;26:523.

    Article  Google Scholar 

  29. Abu-Mugheisib M. Repeated intrathecal triamcinolone acetonide administration in progressive multiple sclerosis: a review. Mult Scler Int. 2011;2011:219049.

    Google Scholar 

  30. Ostergaard M. Intra-articular corticosteroids in arthritic disease: a guide to treatment. BioDrugs. 1998;9(2):95–103.

    Article  CAS  Google Scholar 

  31. Dinarelo CA. Anti-inflammatory agents: present and future. Cell. 2010;140:935.

    Article  Google Scholar 

  32. Gold R. Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders. J Neuroimmunol. 2001;117(1–2):1–8.

    Article  CAS  Google Scholar 

  33. Schoepe S. Glucocorticoid therapy-induced skin atrophy. Exp Dermatol. 2006;15(6):406.

    Article  CAS  Google Scholar 

  34. Gera C. Glucocorticoid-induced osteoporosis: unawareness or negligence in India? Int J Rheum Dis. 2009;12(3):230–3.

    Article  Google Scholar 

  35. Macfarlane DP. Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome. J Endocrinol. 2008;197(2):189–94.

    Article  CAS  Google Scholar 

  36. Peeke PM. Hypercortisolism and obesity. Ann N Y Acad Sci. 1995;29(771):665–6.

    Article  Google Scholar 

  37. De Nicola AF. Regulation of gene expression by corticoid hormones in the brain and spinal Cord. J Steroid Biochem Mol Biol. 1998;65(1–6):253–62.

    Article  Google Scholar 

  38. Hickey T. In vivo evaluation of a dexamethasone/PLGA microsphere system designed to suppress the inflammatory tissue response to implantable medical devices. J Biomed Mater Res. 2002;61:180–7.

    Article  CAS  Google Scholar 

  39. Ciulla TA. Choroidal neovascular membrane inhibition in a laser treated rat model with intraocular sustained release triamcinolone acetonide microimplants. British J Ophthalmol. 2003;87:1032–7.

    Article  CAS  Google Scholar 

  40. Yang CS. An intravitreal sustainedrelease triamcinolone and 5-fluorouracil codrug in the treatment of experimental proliferative vitreoretinopathy. Arch Ophthalmol. 1998;116:69–77.

    CAS  Google Scholar 

  41. Dhanaraju MD. Triamcinolone-loaded glutaraldehyde cross-linked chitosan microspheres: prolonged release approach for the treatment of rheumatoid arthritis. Drug Deliv. 2011;18(3):198–207.

    Article  CAS  Google Scholar 

  42. Mansoor S. Intraocular sustained-release delivery systems for triamcinolone acetonide. Pharma Res. 2009;26(4):770–4.

    Article  CAS  Google Scholar 

  43. The United States Pharmacopeia, 29th edition (USP 29) United States Pharmacopeial Convention Inc., CD-ROM (Insight Publishing Productivity), Rockville, 2006.

  44. Block LH. Solubility and dissolution of triamcinolone acetonide. J Pharm Sci. 1973;62(4):617–21.

    Article  CAS  Google Scholar 

  45. Drabkin DL. Preparations from washed blood cells: Nitric oxide hemoglobin and sulphemoglobin. J Biol Chem. 1935;112:51–6.

    CAS  Google Scholar 

  46. Ferreira MA. Tumor growth, angiogenesis and inflammation in mice lacking receptors for platelet activating factor (PAF). Life Sci. 2007;81:210–7.

    Article  CAS  Google Scholar 

  47. Kuan HC. Synthesis, thermal, mechanical and rheological properties of multiwall carbon nanotube/waterborne polyurethane nanocomposite. Compos Sci Technol. 2005;65(11–12):1703.

    Article  CAS  Google Scholar 

  48. Shan-Hui H. The biocompatibility and antibacterial properties of waterborne polyurethane-silver nanocomposites. Biomaterials. 2010;31(26):6796–8.

    Article  Google Scholar 

  49. Araújo FA. Atorvastatin inhibits inflammatory angiogenesis in mice through down regulation of VEGF, TNF-alpha and TGF-beta1. Biomed Pharmacother. 2010;64(1):29–34.

    Article  Google Scholar 

  50. Pereira IHL. Photopolymerizable and injectable polyurethanes for biomedical applications: synthesis and biocompatibility. Acta Biomater. 2010;6(8):3056–66.

    Article  CAS  Google Scholar 

  51. Thomas V. A new generation of high flex life polyurethane urea for polymer heart valve—studies on in vivo biocompatibility and biodurability. J Biomed Mater Res, Part A. 2008;89(1):192–5.

    Google Scholar 

  52. Oréfice RL. Using the nanostructure of segmented polyurethanes as a template in the fabrication of nanocomposites. Macromolecules. 2005;38:4058.

    Article  Google Scholar 

  53. Chu B. Small-angle X-ray scattering of polymers. Chem Rev. 2001;101(6):1727–32.

    Article  CAS  Google Scholar 

  54. Ping P. Poly(ε-caprolactone) polyurethane and its shape-memory property. Biomacromolecules. 2005;6(2):587–92.

    Article  Google Scholar 

  55. Koberstein JT. Compression-molded polyurethane block copolymers. 1. Microdomain morphology and thermomechanical properties. Macromolecules. 1992;25:6195–204.

    Article  CAS  Google Scholar 

  56. Suchocka-Galas K. The state of ion aggregation in ionomers based on copolymers of styrene and acrylic acid. Eur Polym J. 1998;34:127–32.

    Article  CAS  Google Scholar 

  57. Tatai L. Thermoplastic biodegradable polyurethanes: the effect of chain extender structure on properties and in-vitro degradation. Biomaterials. 2007;28:5407–17.

    Article  CAS  Google Scholar 

  58. Santerre JP. Understanding the biodegradation of polyurethanes: from classical implants to tissue engineering materials. Biomaterials. 2005;26:7457.

    Article  CAS  Google Scholar 

  59. Xavier DO. Metformin inhibits inflammatory angiogenesis in a murine sponge model. Biomed Pharmacother. 2010;64(3):220–5.

    Article  CAS  Google Scholar 

  60. Patan S. Vasculogenesis and angiogenesis. Cancer Treat Res. 2004;117:3–32.

    Article  CAS  Google Scholar 

  61. Campos PP. Mechanisms of wound healing responses in lupus-prone New Zealand White mouse strain. Wound Repair Regen. 2008;16:416–24.

    Article  Google Scholar 

  62. Szekanecz Z. Angiogenesis in rheumatoid arthritis. Autoimmunity. 2009;42(7):563–73.

    Article  CAS  Google Scholar 

  63. Nicosia RF. Paracrine regulation of angiogenesis by different cell types in the aorta ring model. Int J Dev Biol. 2011;55:447–53.

    Article  CAS  Google Scholar 

  64. Aplin AC. Angiopoietin-1 and vascular endothelial growth factor induce expression of inflammatory cytokines before angiogenesis. Physiol Genomics. 2006;27:20–8.

    Article  CAS  Google Scholar 

  65. Gelati M. The angiogenic response of the aorta to injury and inflammatory cytokines requires macrophages. J Immunol. 2008;181:5711–9.

    CAS  Google Scholar 

  66. Emanuel S. A vascular endothelial growth factor receptor-2 kinase inhibitor potentiates the activity of the conventional chemotherapeutic agents paclitaxel and doxorubicin in tumor xenograft models. Mol Pharmacol. 2004;66:635–7.

    Article  CAS  Google Scholar 

  67. Ebrahem Q. Triamcinolone Acetonide Inhibits IL-6- and VEGF-induced angiogenesis downstream of the IL-6 and VEGF receptors. Invest Ophthalmol Vis Sci. 2006;47(11):4935–41.

    Article  Google Scholar 

  68. Khan AI. Lipopolysaccharide: a p38 MAPK-dependent disrupter of neutrophil chemotaxis. Microcirculation. 2005;12:421–2.

    Article  CAS  Google Scholar 

  69. Farias JAC. Modulation of inflammatory processes by leaves extract from Clusia nemorosa both in vitro and in vivo animal models. Inflammation. 2011;1–8. doi:10.1007/s10753-011-9372-y.

  70. Arancibia SA. Toll-like receptors are key participants in innate immune responses. Biol Res. 2007;40:97–102.

    Article  CAS  Google Scholar 

  71. Sadik CD. Neutrophils cascading their way to inflammation. Immunology. 2011;32(1):452–60.

    Google Scholar 

  72. Zhang X. Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophils apoptosis. Eur J Pharmacol. 2001;431:365–71.

    Article  CAS  Google Scholar 

  73. Saffar AS. The molecular mechanisms of glucocorticoids-mediated neutrophil survival. Curr Drug Targets. 2011;12:556–62.

    Article  CAS  Google Scholar 

  74. Barin JG. Macrophage diversity in cardiac inflammation: A review. Immunobiology. 2011;30. doi:10.1016/j.imbio.2011.06.009.

  75. Sundler R. Lysosomal and cytosolic pH as regulators of exocytosis in mouse macrophages. Acta Physiol Scand. 1997;161(4):553–6.

    Article  CAS  Google Scholar 

  76. Barczyk K. Glucocorticoids promote survival of anti-inflammatory macrophages via stimulation of adenosine receptor A3. Blood. 2010;116:446–55.

    Article  CAS  Google Scholar 

  77. Versaci F. Prevention of restenosis after stenting: the emerging role of inflammation. Coron Artery Dis. 2004;15:307–11.

    Article  Google Scholar 

  78. Patil SD. Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis. J Control Release. 2007;117:68–9.

    Article  CAS  Google Scholar 

  79. Belo AV. Murine chemokine CXCL2/KC is a surrogate marker for angiogenic activity in the inflammatory granulation tissue. Microcirculation. 2005;12:597–606.

    Article  CAS  Google Scholar 

  80. Hori Y. Differential effects of angiostatic steroids and dexamethasone on angiogenesis and cytokine levels in rat sponge implants. British J Pharmacol. 1996;118(1584):1.

    Google Scholar 

  81. Stahn C. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008;4:525–33.

    Article  CAS  Google Scholar 

  82. Alangari AA. Genomic and non-genomic actions of glucocorticoids in asthma. Ann Thorac Med. 2010;5(3):133–9.

    Article  Google Scholar 

  83. Basak P. Sustained release of antibiotic from polyurethane coated implant materials. J Mater Sci Mater Med. 2009;20:213–21.

    Article  Google Scholar 

  84. Peyman GA. Delivery systems for intraocular routes. Adv Drug Deliv Rev. 1995;16:107–13.

    Article  CAS  Google Scholar 

  85. Yasukawa T. Drug delivery systems for vitreoretinal diseases. Prog Retin Eye Res. 2004;23:253–61.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the financial support received from the following institutions: FAPEMIG (Minas Gerais—Brazil), CAPES/MEC (Brazil) and CNPq/MCT (Brazil).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gisele Rodrigues Da Silva.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pinto, F.C.H., Da Silva-Cunha Junior, A., Oréfice, R.L. et al. Controlled release of triamcinolone acetonide from polyurethane implantable devices: application for inhibition of inflammatory-angiogenesis. J Mater Sci: Mater Med 23, 1431–1445 (2012). https://doi.org/10.1007/s10856-012-4615-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4615-5

Keywords

Navigation