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The application of layered double hydroxide clay (LDH)-poly(lactide-co-glycolic acid) (PLGA) film composites for the controlled release of antibiotics

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Abstract

Many sites of bacterial infection such as in-dwelling catheters and orthopedic surgical sites require local rather than systemic antibiotic administration. However, currently used controlled release vehicles, such as polymeric films, release water-soluble antibiotics too quickly, whereas nonporous bone cement, used in orthopedics, release very little drug. The purpose of this study was to investigate the use of nanoparticulates composed of layered double hydroxide clays to bind various antibiotics and release them in a controlled manner. Mg–Al (carbonate) layered double hydroxides were synthesized and characterized using established methods. These clay particles were suspended in solutions of the antibiotics tetracycline, doxorubicin (DOX), 5-fluorouracil, vancomycin (VAN), sodium fusidate (SF) and antisense oligonucleotides and binding was determined following centrifugation and quantitation of the unbound fraction by UV/Vis absorbance or HPLC analysis. Drug release from layered double hydroxide clay/drug complexes dispersed in polymeric films was measured by incubation in phosphate-buffered saline (pH 7.4) at 37 °C using absorbance or HPLC analysis. Antimicrobial activity of drug released from film composites was determined using zonal inhibition studies against S. epidermidis. All drugs bound to the clay particles to various degrees. Generally, drugs released with a large burst phase of release (except DOX) with little further drug release after 4 days. Dispersion of drug/clay complexes in poly(lactic-co-glycolic acid) films resulted in a reduced burst phase of release and a slow continuous release for many weeks with effective antimicrobial amounts of VAN and SF released at later time points. Layered double hydroxide clays may be useful for controlled release applications at sites requiring long-term antibiotic exposure as they maintain the drug in a non-degraded state and release effective amounts of drug over long time periods. LDH clay/drug complexes are amenable to homogenous dispersion in polymeric films where implant coating may be optimal or required.

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References

  1. Li F, Duan X. Layered double hydroxides. Structure and Bonding. Vol.119. In: Duan, Xue, Evans, David G (editors) Applications of layered double hydroxides. Berlin: Springer; 2006. XII.

  2. Tarnawski A, Pai R, Itani R, Wyle FA. The antacid Talcid adsorbs and neutralizes all proteins secreted by H. pylori including VacA cytotoxin: a new mechanism for its ulcer-healing action? Digestion. 1999;60(5):449–55.

    Article  CAS  Google Scholar 

  3. Aguzzi C, Cerezo P, Viseras C, Caramella C. Use of clays as drug delivery systems: possibilities and limitations. Appl Clay Sci. 2007;36(1–3):22–36. doi:10.1016/j.clay.2006.06.015.

    Article  CAS  Google Scholar 

  4. Mohanambe L, Vasudevan S. Anionic clays containing anti-inflammatory drug molecules: comparison of molecular dynamics simulation and measurements. J Phys Chem B. 2005;109(32):15651–8. doi:10.1021/jp050480m.

    Article  CAS  Google Scholar 

  5. Li B, He J, Evans DG, Duan X. Inorganic layered double hydroxides as a drug delivery system—intercalation and in vitro release of fenbufen. Appl Clay Sci. 2004;27(3–4):199–207. doi:10.1016/j.clay.2004.07.002.

    Article  Google Scholar 

  6. Khan AI, O’Hare D. Intercalation chemistry of layered double hydroxides: recent developments and applications. J Mater Chem. 2002;12(11):3191–8. doi:10.1039/b204076j.

    Article  CAS  Google Scholar 

  7. Ambrogi V, Fardella G, Grandolini G, Perioli L. Intercalation compounds of hydrotalcite—like anionic clays with antiinflammatory agents-I. Intercalation and in vitro release of ibuprofen. Int J Pharm. 2001;220(1–2):23–32.

    Article  CAS  Google Scholar 

  8. Gordijo CuR, Barbosa CsAs, Da Costa Ferreira AM, Constantino VRL, Oliveira Silva Dd. Immobilization of ibuprofen and copper-ibuprofen drugs on layered double hydroxides. J Pharm Sci. 2005;94(5):1135–48. doi:10.1002/jps.20336.

    Article  CAS  Google Scholar 

  9. Kong X, Jin L, Wei M, Duan X. Antioxidant drugs intercalated into layered double hydroxide: structure and in vitro release. Appl Clay Sci. 2010;49(3):324–9. doi:10.1016/j.clay.2010.06.017.

    Article  CAS  Google Scholar 

  10. Viseras C, Cerezo P, Sanchez R, Salcedo I, Aguzzi C. Current challenges in clay minerals for drug delivery. Appl Clay Sci. 2010;48(3):291–5. doi:10.1016/j.clay.2010.01.007.

    Article  CAS  Google Scholar 

  11. Trikeriotis M, Ghanotakis DF. Intercalation of hydrophilic and hydrophobic antibiotics in layered double hydroxides. Int J Pharm. 2007;332(1–2):176–84. doi:10.1016/j.ijpharm.2006.09.031.

    Article  CAS  Google Scholar 

  12. Ryu S-J, Jung H, Oh J-M, Lee J-K, Choy J-H. Layered double hydroxide as novel antibacterial drug delivery system. J Phys Chem Solids. 2010;71(4):685–8. doi:10.1016/j.jpcs.2009.12.066.

    Article  CAS  Google Scholar 

  13. Tammaro L, Costantino U, Bolognese A, Sammartino G, Marenzi G, Calignano A, et al. Nanohybrids for controlled antibiotic release in topical applications. Int J Antimicrob Agents. 2007;29(4):417–23. doi:10.1016/j.ijantimicag.2006.11.019.

    Article  CAS  Google Scholar 

  14. Knetsch MLW, Koole LH. New strategies in the development of antimicrobial coatings: the example of increasing usage of silver and silver nanoparticles. Polymers. 2011;3(1):340–66. doi:10.3390/polym3010340.

    Article  CAS  Google Scholar 

  15. Ramritu P, Halton K, Collignon P, Cook D, Fraenkel D, Battistutta D, et al. A systematic review comparing the relative effectiveness of antimicrobial-coated catheters in intensive care units. Am J Infect Control. 2008;36(2):104–17. doi:10.1016/j.ajic.2007.02.012.

    Article  Google Scholar 

  16. Wu P, Grainger DW. Drug/device combinations for local drug therapies and infection prophylaxis. Biomaterials. 2006;27(11):2450–67. doi:10.1016/j.biomaterials.2005.11.031.

    Article  CAS  Google Scholar 

  17. Jackson J, Leung F, Duncan C, Mugabe C, Burt H. The use of bone cement for the localized, controlled release of the antibiotics vancomycin, linezolid, or fusidic acid: effect of additives on drug release rates and mechanical strength. Drug Deliv Transl Res. 2011;1(2):121–31. doi:10.1007/s13346-011-0015-5.

    Article  CAS  Google Scholar 

  18. Andollina A, Bertoni G, Zolezzi C, Trentani F, Trentani P, Maria Borrelli A, et al. Vancomycin and meropenem in acrylic cement: elution kinetics of in vitro bactericidal action. Chir Organi Mov. 2008;91(3):153–8. doi:10.1007/s12306-007-0025-0.

    Article  Google Scholar 

  19. Chakraborti M, Jackson JK, Plackett D, Brunette DM, Burt HM. Drug intercalation in layered double hydroxide clay: application in the development of a nanocomposite film for guided tissue regeneration. Int J Pharm. 2011;416(1):305–13. doi:10.1016/j.ijpharm.2011.06.016.

    CAS  Google Scholar 

  20. Long KA, Jackson JK, Yang C, Chehroudi B, Brunette DM, Burt HM. Controlled release of alendronate from polymeric films. J Biomater Sci Polym Ed. 2009;20(5–6):653–72. doi:10.1163/156856209X426457.

    Article  CAS  Google Scholar 

  21. Woodford N, Wareham DW. Tackling antibiotic resistance: a dose of common antisense? J Antimicrob Chemother. 2008;63(2):225–9. doi:10.1093/jac/dkn467.

    Article  Google Scholar 

  22. Chopra I. Prospects for antisense agents in the therapy of bacterial infections. Expert Opin Investig Drugs. 1999;8(8):1203–8. doi:10.1517/13543784.8.8.1203.

    Article  CAS  Google Scholar 

  23. Springate CM, Jackson JK, Gleave ME, Burt HM. Clusterin antisense complexed with chitosan for controlled intratumoral delivery. Int J Pharm. 2008;350(1–2):53–64. doi:10.1016/j.ijpharm.2007.08.018.

    Article  CAS  Google Scholar 

  24. Ambrogi V, Fardella G, Grandolini G, Perioli L, Tiralti MC. Intercalation compounds of hydrotalcite—like anionic clays with anti-inflammatory agents, II: uptake of diclofenac for a controlled release formulation. AAPS Pharm Sci Tech. 2002;3(3):E26. doi:10.1208/pt030326.

    Article  Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada

    Michelle Chakraborti, John K. Jackson, Samuel E. Gilchrist & Helen M. Burt

  2. Danish Polymer Center, Department of Chemical Engineering, Technical University of Denmark, Building 229, Søltofts Plads, 2800 Kgs., Lyngby, Denmark

    David Plackett

Authors
  1. Michelle Chakraborti
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  2. John K. Jackson
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  3. David Plackett
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  4. Samuel E. Gilchrist
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  5. Helen M. Burt
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Correspondence to John K. Jackson.

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Chakraborti, M., Jackson, J.K., Plackett, D. et al. The application of layered double hydroxide clay (LDH)-poly(lactide-co-glycolic acid) (PLGA) film composites for the controlled release of antibiotics. J Mater Sci: Mater Med 23, 1705–1713 (2012). https://doi.org/10.1007/s10856-012-4638-y

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  • DOI: https://doi.org/10.1007/s10856-012-4638-y

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