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A controlled release of antibiotics from calcium phosphate-coated poly(lactic-co-glycolic acid) particles and their in vitro efficacy against Staphylococcus aureus biofilm

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Abstract

Ceramic-polymer hybrid particles, intended for osteomyelitis treatment, were fabricated by preparing poly(lactic-co-glycolic acid) particles through an emulsion solvent evaporation technique, followed by calcium phosphate (CaP) coating via a surface adsorption-nucleation method. The presence of CaP coating on the surface of the particles was confirmed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. Subsequently, two antibiotics for treating bone infection, nafcillin (hydrophilic) and levofloxacin (amphiphilic), were loaded into these hybrid particles and their in vitro drug release studies were investigated. The CaP coating was shown to reduce burst release, while providing sustained release of the antibiotics for up to 4 weeks. In vitro bacterial study against Staphylococcus aureus demonstrated the capability of these antibiotic-loaded hybrid particles to inhibit biofilm formation as well as deteriorate established biofilm, making this hybrid system a potential candidate for further investigation for osteomyelitis treatment.

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References

  1. Di Silvio L, Bonfield W. Biodegradable drug delivery system for the treatment of bone infection and repair. J Mater Sci. 1999;10:653–8.

    Google Scholar 

  2. Liu HN, Webster TJ. Ceramic/polymer nanocomposites with tunable drug delivery capability at specific disease sites. J Biomed Mater Res A. 2009;93A:1180–92.

    Google Scholar 

  3. Nandi SK, Mukherjee P, Roy S, Kundu B, De DK, Basu D. Local antibiotic delivery systems for the treatment of osteomyelitis—a review. Mater Sci Eng C. 2009;29:2478–85.

    Article  Google Scholar 

  4. Naraharisetti PK, Lew MDN, Fu YC, Lee DJ, Wang CH. Gentamicin-loaded discs and microspheres and their modifications: characterization and in vitro release. J Control Release. 2005;102:345–59.

    Article  Google Scholar 

  5. Billon A, Chabaud L, Gouyette A, Bouler JM, Merle C. Vancomycin biodegradable poly(lactide-co-glycolide) microparticles for bone implantation. Influence of the formulation parameters on the size, morphology, drug loading and in vitro release. J Microencapsul. 2005;22:841–52.

    Article  Google Scholar 

  6. Xu QG, Czemuszka JI. Controlled release of amoxicillin from hydroxyapatite-coated poly(lactic-co-glycolic acid) microspheres. J Control Release. 2008;127:146–53.

    Article  Google Scholar 

  7. Schnieders J, Gbureck U, Thull R, Kissel T. Controlled release of gentamicin from calcium phosphate—poly(lactic acid-co-glycolic acid) composite bone cement. Biomaterials. 2006;27:4239–49.

    Article  Google Scholar 

  8. Kanellakopoulou K, Thivaios GC, Kolia M, Dontas I, Nakopoulou L, Dounis E, et al. Local treatment of experimental Pseudomonas aeruginosa osteomyelitis with a biodegradable dilactide polymer releasing ciprofloxacin. Antimicrob Agents Chemother. 2008;52:2335–9.

    Article  Google Scholar 

  9. Jain AK, Panchagnula R. Skeletal drug delivery systems. Int J Pharm. 2000;206:1–12.

    Article  Google Scholar 

  10. Glowka E, Sapin-Minet A, Leroy P, Lulek J, Maincent P. Preparation and in vitro-in vivo evaluation of salmon calcitonin-loaded polymeric nanoparticles. J Microencapsul. 2010;27:25–36.

    Article  Google Scholar 

  11. Li Y, Lim S, Ooi C. Fabrication of cisplatin-loaded poly(lactide-co-glycolide) composite microspheres for osteosarcoma treatment. Pharm Res. 2012;29:756–69.

    Article  Google Scholar 

  12. Rhee SH, Lee SJ. Effect of acidic degradation products of poly(lactic-co-glycolic)acid on the apatite-forming ability of poly(lactic-co-glycolic)acid-siloxane nanohybrid material. J Biomed Mater Res A. 2007;83A:799–805.

    Article  Google Scholar 

  13. Kang SW, Yang HS, Seo SW, Han DK, Kim BS. Apatite-coated poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for bone tissue engineering. J Biomed Mater Res A. 2008;85A:747–56.

    Article  Google Scholar 

  14. Loo SCJ, Moore T, Banik B, Alexis F. Biomedical applications of hydroxyapatite nanoparticles. Curr Pharm Biotechnol. 2010;11:333–42.

    Article  Google Scholar 

  15. Suzuki O. Interface of synthetic inorganic biomaterials and bone regeneration. Int Congr Ser. 2005;1284:274–83.

    Article  Google Scholar 

  16. Joosten U, Joist A, Gosheger G, Liljenqvist U, Brandt B, von Eiff C. Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis. Biomaterials. 2005;26:5251–8.

    Article  Google Scholar 

  17. Herrmann M, Vaudaux PE, Pittet D, Auckenthaler R, Lew PD, Perdreau FS, et al. Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material. J Infect Dis. 1988;158:693–701.

    Article  Google Scholar 

  18. Lucke M, Schmidmaier G, Sadoni S, Wildemann B, Schiller R, Stemberger A, et al. A new model of implant-related osteomyelitis in rats. J Biomed Mater Res B. 2003;67B:593–602.

    Article  Google Scholar 

  19. Davis JS. Management of bone and joint infections due to Staphylococcus aureus. Internal Med. 2005;35:S79–96.

    Article  Google Scholar 

  20. Lee WL, Loei C, Widjaja E, Loo SCJ. Altering the drug release profiles of double-layered ternary-phase microparticles. J Control Release. 2011;151:229–38.

    Article  Google Scholar 

  21. Lee WL, Yu P-O, Hong M, Widjaja E, Loo SCJ. Designing multilayered particulate systems for tunable drug release profiles. Acta Biomater. 2012;8:2271–8.

    Article  Google Scholar 

  22. French GL. Staphylococcal sepsis: treatment ELS. New York: Wiley; 2001.

    Google Scholar 

  23. Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med. 1997;336:999–1007.

    Article  Google Scholar 

  24. Croom KF, Goa KL. Levofloxacin: a review of its use in the treatment of bacterial infections in the United States. Drugs. 2003;63:2769–802.

    Article  Google Scholar 

  25. Koort JK, Makinen TJ, Suokas E, Veiranto M, Jalava J, Knuuti J, et al. Efficacy of ciprofloxacin-releasing bioabsorbable osteoconductive bone defect filler for treatment of experimental osteomyelitis due to Staphylococcus aureus. Antimicrob Agents Chemother. 2005;49:1502–8.

    Article  Google Scholar 

  26. Virto MR, Elorza B, Torrado S, Elorza MDA, Frutos G. Improvement of gentamicin poly(d, l-lactic-co-glycolic acid) microspheres for treatment of osteomyelitis induced by orthopedic procedures. Biomaterials. 2007;28:877–85.

    Article  Google Scholar 

  27. Wimer SM, Schoonover L, Garrison MW. Levofloxacin: a therapeutic review. Clin Ther. 1998;20:1049–70.

    Article  Google Scholar 

  28. Wiegand I, Hilpert K, Hancock REW. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protocols. 2008;3:163–75.

    Article  Google Scholar 

  29. Neut D, Kluin OS, Crielaard BJ, van der Mei HC, Busscher HJ, Grijpma DW. A biodegradable antibiotic delivery system based on poly-(trimethylene carbonate) for the treatment of osteomyelitis. Acta Orthopedica. 2009;80(5):514–9.

    Article  Google Scholar 

  30. Kwasny SM, Opperman TJ. Static biofilm cultures of gram-positive pathogens grown in a microtiter format used for anti-biofilm drug discovery. Current Protocols in Pharmacology. New York: Wiley; 2001.

    Google Scholar 

  31. Shalaby S, Marc S. Polymeric controlled release systems for management of bone infection. Polymers for Dental and Orthopedic Applications. Boca Raton: CRC Press; 2006. p. 391–411.

    Chapter  Google Scholar 

  32. Ito F, Fujimori H, Makino K. Factors affecting the loading efficiency of water-soluble drugs in PLGA microspheres. Colloids Surf B. 2008;61:25–9.

    Article  Google Scholar 

  33. Xu Q, Crossley A, Czernuszka J. Preparation and characterization of negatively charged poly(lactic-co-glycolic acid) microspheres. J Pharm Sci. 2009;98:2377–89.

    Article  Google Scholar 

  34. Astete CE, Sabliov CM. Synthesis and characterization of PLGA nanoparticles. J Biomater Sci. 2006;17:247–89.

    Article  Google Scholar 

  35. Choi S-W, Zhang Y, Xia Y. Fabrication of microbeads with a controllable hollow interior and porous wall using a capillary fluidic device. Adv Funct Mater. 2009;19:2943–9.

    Article  Google Scholar 

  36. Chaisri W, Ghassemi AH, Hennink WE, Okonogi S. Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters. Colloids Surf B. 2011;84:508–14.

    Article  Google Scholar 

  37. Frick A, Möller H, Wirbitzki E. Biopharmaceutical characterization of oral immediate release drug products. In vitro/in vivo comparison of phenoxymethylpenicillin potassium, glimepiride and levofloxacin. Eur J Pharm Biopharm. 1998;46:305–11.

    Article  Google Scholar 

  38. Lee ES, Kwon MJ, Lee H, Kim JJ. Stabilization of protein encapsulated in poly(lactide-co-glycolide) microspheres by novel viscous S/W/O/W method. Int J Pharm. 2007;331:27–37.

    Article  Google Scholar 

  39. Wischke C, Schwendeman SP. Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm. 2008;364:298–327.

    Article  Google Scholar 

  40. Jongpaiboonkit L, Franklin-Ford T, Murphy WL. Growth of hydroxyapatite coatings on biodegradable polymer microspheres. ACS Appl Mater Interfaces. 2009;1:1504–11.

    Article  Google Scholar 

  41. Taguchi T, Muraoka Y, Matsuyama H, Kishida A, Akashi M. Apatite coating on hydrophilic polymer-grafted poly(ethylene) films using an alternate soaking process. Biomaterials. 2001;22:53–8.

    Article  Google Scholar 

  42. Fujihara K, Kotaki M, Ramakrishna S. Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers. Biomaterials. 2005;26:4139–47.

    Article  Google Scholar 

  43. Boutinguiza M, Pou J, Lusquiños F, Comesaña R, Riveiro A. Laser-assisted production of tricalcium phosphate nanoparticles from biological and synthetic hydroxyapatite in aqueous medium. Appl Surf Sci. 2011;257:5195–9.

    Article  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the National Medical Research Council (NMRC: NMRC/EDG/0062/2009), A*STAR (Project No: 102 129 0098), and the National Research Foundation (NRF) and Ministry of Education, Singapore (MOE) under its Research Centre of Excellence Programme, Singapore Centre on Environmental Life Sciences Engineering (SCELSE) (M4220001.C70) and the Start-up Grants (M020070200) from Nanyang Technological University, Singapore.

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Correspondence to Sierin Lim or Say Chye Joachim Loo.

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Bastari, K., Arshath, M., NG, Z.H.M. et al. A controlled release of antibiotics from calcium phosphate-coated poly(lactic-co-glycolic acid) particles and their in vitro efficacy against Staphylococcus aureus biofilm. J Mater Sci: Mater Med 25, 747–757 (2014). https://doi.org/10.1007/s10856-013-5125-9

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  • DOI: https://doi.org/10.1007/s10856-013-5125-9

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