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.
Similar content being viewed by others
References
Ayres E. Phase morphology of hydrolysable polyurethanes derived from aqueous dispersions. Eur Polym J. 2007;43:3510–1.
Da Silva GR. Biodegradation of polyurethanes and nanocomposites to non-cytotoxic degradation products. Polym Degrad Stabil. 2010;95(4):491–9.
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.
Zhang C. Synthesis and characterization of biocompatible, degradable, light curable, polyurethane-based elastic hydrogels. J Biomed Mater Res. 2007;82(3):637.
Laschke MW. In vivo biocompatibility and vascularization of biodegradable porous polyurethane scaffolds for tissue engineering. Acta Biomater. 2009;5:1991–2001.
Hausner T. Nerve regeneration using tubular scaffolds from biodegradable polyurethane. Acta Neurochir Suppl. 2007;100:69–72.
Tongkui C. Rapid prototyping of a double-layer polyurethane-collagen conduit for peripheral nerve regeneration. Tissue Eng Part C Methods. 2009;15:1–9.
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.
Grenier S. Polyurethane biomaterials for fabricating 3D porous scaffolds and supporting vascular cells. J Biomed Mater Res, Part A. 2007;82:802–9.
Zhang L. A novel small-diameter vascular graft: in vivo behavior of biodegradable three-layered tubular scaffolds. Biotechnol Bioeng. 2008;99:1007–15.
Lee CR. Fibrinpolyurethane composites for articular cartilage tissue engineering: a preliminary analysis. Tissue Eng. 2005;11:1562–3.
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.
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.
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.
Bil M. Optimization of the structure of polyurethanes for bone tissue engineering applications. Acta Biomater. 2010;6(7):2501.
Ryszkowska JL. Biodegradable polyurethane composite scaffolds containing Bioglass® for bone tissue engineering. Acta Biomater. 2010;6(7):2484–93.
Omar S. Colon-specific drug delivery for mebeverine hydrochloride. J Drug Target. 2007;15(10):691.
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.
Da Silva GR. Controlled release of dexamethasone acetate from biodegradable and biocompatible polyurethane and polyurethane nanocomposite. J Drug Target. 2009;17(5):374–83.
Donelli G. Efficacy of antiadhesive, antibiotic and antiseptic coatings in preventing catheter-related infections: review. J Chemother. 2001;13:595.
Francolini I. Polyurethane anionomers containing metal ions with antimicrobial properties: thermal, mechanical and biological characterization. Acta Biomater. 2010;6:3482.
Huynh TTN. Characterization of a polyurethane-based controlled release system for local delivery of chlorhexidine diacetate. Eur J Pharma Biopharm. 2010;74:255–64.
Johnson T. Design of intravaginal ring for simultaneous delivery of antiretroviral drugs. Antiviral Res. 2009;82(2):A74.
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.
Da Silva GR. Biodegradable polyurethane nanocomposites containing dexamethasone for ocular route. Mater Sci Eng, C. 2011;31(2):414–22.
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.
Sivak WN. Simultaneous drug release at different rates from biodegradable polyurethane foams. Acta Biomater. 2009;5(7):2398–408.
Kim H. Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration. Retina. 2006;26:523.
Abu-Mugheisib M. Repeated intrathecal triamcinolone acetonide administration in progressive multiple sclerosis: a review. Mult Scler Int. 2011;2011:219049.
Ostergaard M. Intra-articular corticosteroids in arthritic disease: a guide to treatment. BioDrugs. 1998;9(2):95–103.
Dinarelo CA. Anti-inflammatory agents: present and future. Cell. 2010;140:935.
Gold R. Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders. J Neuroimmunol. 2001;117(1–2):1–8.
Schoepe S. Glucocorticoid therapy-induced skin atrophy. Exp Dermatol. 2006;15(6):406.
Gera C. Glucocorticoid-induced osteoporosis: unawareness or negligence in India? Int J Rheum Dis. 2009;12(3):230–3.
Macfarlane DP. Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome. J Endocrinol. 2008;197(2):189–94.
Peeke PM. Hypercortisolism and obesity. Ann N Y Acad Sci. 1995;29(771):665–6.
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.
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.
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.
Yang CS. An intravitreal sustainedrelease triamcinolone and 5-fluorouracil codrug in the treatment of experimental proliferative vitreoretinopathy. Arch Ophthalmol. 1998;116:69–77.
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.
Mansoor S. Intraocular sustained-release delivery systems for triamcinolone acetonide. Pharma Res. 2009;26(4):770–4.
The United States Pharmacopeia, 29th edition (USP 29) United States Pharmacopeial Convention Inc., CD-ROM (Insight Publishing Productivity), Rockville, 2006.
Block LH. Solubility and dissolution of triamcinolone acetonide. J Pharm Sci. 1973;62(4):617–21.
Drabkin DL. Preparations from washed blood cells: Nitric oxide hemoglobin and sulphemoglobin. J Biol Chem. 1935;112:51–6.
Ferreira MA. Tumor growth, angiogenesis and inflammation in mice lacking receptors for platelet activating factor (PAF). Life Sci. 2007;81:210–7.
Kuan HC. Synthesis, thermal, mechanical and rheological properties of multiwall carbon nanotube/waterborne polyurethane nanocomposite. Compos Sci Technol. 2005;65(11–12):1703.
Shan-Hui H. The biocompatibility and antibacterial properties of waterborne polyurethane-silver nanocomposites. Biomaterials. 2010;31(26):6796–8.
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.
Pereira IHL. Photopolymerizable and injectable polyurethanes for biomedical applications: synthesis and biocompatibility. Acta Biomater. 2010;6(8):3056–66.
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.
Oréfice RL. Using the nanostructure of segmented polyurethanes as a template in the fabrication of nanocomposites. Macromolecules. 2005;38:4058.
Chu B. Small-angle X-ray scattering of polymers. Chem Rev. 2001;101(6):1727–32.
Ping P. Poly(ε-caprolactone) polyurethane and its shape-memory property. Biomacromolecules. 2005;6(2):587–92.
Koberstein JT. Compression-molded polyurethane block copolymers. 1. Microdomain morphology and thermomechanical properties. Macromolecules. 1992;25:6195–204.
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.
Tatai L. Thermoplastic biodegradable polyurethanes: the effect of chain extender structure on properties and in-vitro degradation. Biomaterials. 2007;28:5407–17.
Santerre JP. Understanding the biodegradation of polyurethanes: from classical implants to tissue engineering materials. Biomaterials. 2005;26:7457.
Xavier DO. Metformin inhibits inflammatory angiogenesis in a murine sponge model. Biomed Pharmacother. 2010;64(3):220–5.
Patan S. Vasculogenesis and angiogenesis. Cancer Treat Res. 2004;117:3–32.
Campos PP. Mechanisms of wound healing responses in lupus-prone New Zealand White mouse strain. Wound Repair Regen. 2008;16:416–24.
Szekanecz Z. Angiogenesis in rheumatoid arthritis. Autoimmunity. 2009;42(7):563–73.
Nicosia RF. Paracrine regulation of angiogenesis by different cell types in the aorta ring model. Int J Dev Biol. 2011;55:447–53.
Aplin AC. Angiopoietin-1 and vascular endothelial growth factor induce expression of inflammatory cytokines before angiogenesis. Physiol Genomics. 2006;27:20–8.
Gelati M. The angiogenic response of the aorta to injury and inflammatory cytokines requires macrophages. J Immunol. 2008;181:5711–9.
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.
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.
Khan AI. Lipopolysaccharide: a p38 MAPK-dependent disrupter of neutrophil chemotaxis. Microcirculation. 2005;12:421–2.
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.
Arancibia SA. Toll-like receptors are key participants in innate immune responses. Biol Res. 2007;40:97–102.
Sadik CD. Neutrophils cascading their way to inflammation. Immunology. 2011;32(1):452–60.
Zhang X. Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophils apoptosis. Eur J Pharmacol. 2001;431:365–71.
Saffar AS. The molecular mechanisms of glucocorticoids-mediated neutrophil survival. Curr Drug Targets. 2011;12:556–62.
Barin JG. Macrophage diversity in cardiac inflammation: A review. Immunobiology. 2011;30. doi:10.1016/j.imbio.2011.06.009.
Sundler R. Lysosomal and cytosolic pH as regulators of exocytosis in mouse macrophages. Acta Physiol Scand. 1997;161(4):553–6.
Barczyk K. Glucocorticoids promote survival of anti-inflammatory macrophages via stimulation of adenosine receptor A3. Blood. 2010;116:446–55.
Versaci F. Prevention of restenosis after stenting: the emerging role of inflammation. Coron Artery Dis. 2004;15:307–11.
Patil SD. Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis. J Control Release. 2007;117:68–9.
Belo AV. Murine chemokine CXCL2/KC is a surrogate marker for angiogenic activity in the inflammatory granulation tissue. Microcirculation. 2005;12:597–606.
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.
Stahn C. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008;4:525–33.
Alangari AA. Genomic and non-genomic actions of glucocorticoids in asthma. Ann Thorac Med. 2010;5(3):133–9.
Basak P. Sustained release of antibiotic from polyurethane coated implant materials. J Mater Sci Mater Med. 2009;20:213–21.
Peyman GA. Delivery systems for intraocular routes. Adv Drug Deliv Rev. 1995;16:107–13.
Yasukawa T. Drug delivery systems for vitreoretinal diseases. Prog Retin Eye Res. 2004;23:253–61.
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
Corresponding author
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10856-012-4615-5