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Drug Delivery and Translational Research

, Volume 3, Issue 6, pp 542–550 | Cite as

Zein/polycaprolactone electrospun matrices for localised controlled delivery of tetracycline

  • Nour Alhusein
  • Ian S. Blagbrough
  • Paul A. De BankEmail author
Research Article

Abstract

We report the controlled release of the antibiotic tetracycline (Tet) from triple-layered (3L) electrospun matrices consisting of zein or a zein/PCL blend, where the drug was loaded into the central layer with the two outer layers acting as diffusion barriers. These fibrous matrices successfully encapsulated Tet and efficiently inhibited the growth of a clinical isolate, the methicillin-resistant Staphylococcus aureus strain MRSA252, as demonstrated in a modified Kirby–Bauer disc assay over 5 days. Whilst untreated zein fibres are unstable in an aqueous environment, rapidly shrinking due to plasticisation and film formation, blending zein with PCL stabilised the electrospun matrices and prevented them from shrinking. These 3L formulations display sustained antibiotic release and provide a proof of concept for zein-based polymeric matrices as wound dressings to treat or prevent bacterial infection. This is the first demonstration of the controlled release of a clinically used antibiotic from electrospun zein-based matrices.

Keywords

Antibiotic Drug delivery Electrospinning Raman microscopy Sustained release Wound dressing 

Notes

Acknowledgements

We thank Damascus University for a fully funded scholarship (to NA). We thank Ursula Potter (SEM), John Mitchels (Raman microscopy) and Jo Carter (Microbiology), all at the University of Bath, for their skilled support.

Conflict of interest

All three authors Nour Alhusein, Ian S. Blagbrough and Paul A. De Bank declare that they have no conflict of interest. There were no experiments on human or animal subjects.

References

  1. 1.
    Bognitzki M, Czado W, Frese T, Schaper A, Hellwig M, Steinhart M, et al. Nanostructured fibers via electrospinning. Adv Mater. 2001;13:70–2.CrossRefGoogle Scholar
  2. 2.
    Wang H-S, Fu G-D, Li X-S. Functional polymeric nanofibers from electrospinning. Recent Pat Nanotech. 2009;3:21–31.CrossRefGoogle Scholar
  3. 3.
    Li D, Xia Y. Direct fabrication of composite and ceramic hollow nanofibers by electrospinning. Nano Lett. 2004;4:933–8.CrossRefGoogle Scholar
  4. 4.
    Jiang H, Hu Y, Li Y, Zhao P, Zhu K, Chen W. A facile technique to prepare biodegradable coaxial electrospun nanofibers for controlled release of bioactive agents. J Control Release. 2005;108:237–43.PubMedCrossRefGoogle Scholar
  5. 5.
    Huang ZM, Zhang YZ, Kotaki M, Ramakrishna S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos Sci Technol. 2003;63:2223–53.CrossRefGoogle Scholar
  6. 6.
    Pham QP, Sharma U, Mikos AG. Electrospinning of polymeric nanofibers for tissue engineering applications: a review. Tissue Eng. 2006;12:1197–211.PubMedCrossRefGoogle Scholar
  7. 7.
    Sill TJ, Recum von HA. Electrospinning: applications in drug delivery and tissue engineering. Biomaterials. 2008;29:1989–2006.PubMedCrossRefGoogle Scholar
  8. 8.
    Meinel AJ, Germershaus O, Luhmann T, Merkle HP, Meinel L. Electrospun matrices for localized drug delivery: current technologies and selected biomedical applications. Eur J Pharm Biopharm. 2012;81:1–13.PubMedCrossRefGoogle Scholar
  9. 9.
    Goh Y-F, Shakir I, Hussain R. Electrospun fibers for tissue engineering, drug delivery, and wound dressing. J Mater Sci. 2013;48:3027–54.CrossRefGoogle Scholar
  10. 10.
    Fullana MJ, Wnek GE. Electrospun collagen and its applications in regenerative medicine. Drug Deliv Transl Res. 2012;2:313–22.CrossRefGoogle Scholar
  11. 11.
    Ji W, Sun Y, Yang F, van den Beucken JJJP, Fan M, Chen Z, et al. Bioactive electrospun scaffolds delivering growth factors and genes for tissue engineering applications. Pharm Res. 2011;28:1259–72.PubMedCrossRefGoogle Scholar
  12. 12.
    Ignatova M, Rashkov I, Manolova N. Drug-loaded electrospun materials in wound-dressing applications and in local cancer treatment. Expert Opin Drug Deliv. 2013;10:469–83.PubMedCrossRefGoogle Scholar
  13. 13.
    Alhusein N, Blagbrough IS, De Bank PA. Electrospun matrices for localised controlled drug delivery: release of tetracycline hydrochloride from layers of polycaprolactone and poly(ethylene-co-vinyl acetate). Drug Deliv Transl Res. 2012;2:477–88.CrossRefGoogle Scholar
  14. 14.
    Alhusein N, De Bank PA, Blagbrough IS, Bolhuis A. Killing bacteria within biofilms by sustained release of tetracycline from triple-layered electrospun micro/nanofibre matrices of polycaprolactone and poly(ethylene-co-vinyl acetate). Drug Deliv Transl Res. 2013. doi: 10.1007/s13346-013-0164-9.
  15. 15.
    Ruckh TT, Oldinski RA, Carroll DA, Mikhova K, Bryers JD, Popat KC. Antimicrobial effects of nanofiber poly(caprolactone) tissue scaffolds releasing rifampicin. J Mater Sci Mater Med. 2012;23:1411–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Lee KY, Jeong L, Kang YO, Lee SJ, Park WH. Electrospinning of polysaccharides for regenerative medicine. Adv Drug Deliv Rev. 2009;61:1020–32.PubMedCrossRefGoogle Scholar
  17. 17.
    Sun Q-S, Dong J, Lin Z-X, Yang B, Wang J-Y. Comparison of cytocompatibility of zein film with other biomaterials and its degradability in vitro. Biopolymers. 2005;78:268–74.PubMedCrossRefGoogle Scholar
  18. 18.
    Dong J, Sun Q, Wang J-Y. Basic study of corn protein, zein, as a biomaterial in tissue engineering, surface morphology and biocompatibility. Biomaterials. 2004;25:4691–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Salerno A, Oliviero M, Di Maio E, Netti PA, Rofani C, Colosimo A, et al. Design of novel three-phase PCL/TZ-HA biomaterials for use in bone regeneration applications. J Mater Sci Mater Med. 2010;21:2569–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Tu J, Wang H, Li H, Dai K, Wang J, Zhang X. The in vivo bone formation by mesenchymal stem cells in zein scaffolds. Biomaterials. 2009;30:4369–76.PubMedCrossRefGoogle Scholar
  21. 21.
    Qu Z-H, Wang H-J, Tang T-T, Zhang X-L, Wang J-Y, Dai K-R. Evaluation of the zein/inorganics composite on biocompatibility and osteoblastic differentiation. Acta Biomater. 2008;4:1360–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Wang H-J, Gong S-J, Lin Z-X, Fu J-X, Xue S-T, Huang J-C, et al. In vivo biocompatibility and mechanical properties of porous zein scaffolds. Biomaterials. 2007;28:3952–64.PubMedCrossRefGoogle Scholar
  23. 23.
    Miyoshi T, Toyohara K, Minematsu H. Preparation of ultrafine fibrous zein membranes via electrospinning. Polym Int. 2005;54:1187–90.CrossRefGoogle Scholar
  24. 24.
    Lin L, Perets A, Har-El YE, Varma D, Li M, Lazarovici P, Woerdeman DL, Lelkes PI. Alimentary “green” proteins as electrospun scaffolds for skin regenerative engineering. J Tissue Eng Regen Med. 2012. doi: 10.1002/term.1493.
  25. 25.
    Lin J, Li C, Zhao Y, Hu J, Zhang L-M. Co-electrospun nanofibrous membranes of collagen and zein for wound healing. ACS Appl Mater Interfaces. 2012;4:1050–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Liu X, Sun Q, Wang H, Zhang L, Wang J-Y. Microspheres of corn protein, zein, for an ivermectin drug delivery system. Biomaterials. 2005;26:109–15.PubMedCrossRefGoogle Scholar
  27. 27.
    Mehta SK, Kaur G, Verma A. Fabrication of plant protein microspheres for encapsulation, stabilization and in vitro release of multiple anti-tuberculosis drugs. Colloids Surf A Physicochem Eng Asp. 2011;375:219–30.CrossRefGoogle Scholar
  28. 28.
    de Sousa FO, Blanco-Méndez J, Pérez-Estévez A, Seoane-Prado R, Luzardo-Álvarez A. Effect of zein on biodegradable inserts for the delivery of tetracycline within periodontal pockets. J Biomater Appl. 2012;27:187–200.PubMedCrossRefGoogle Scholar
  29. 29.
    Karthikeyan K, Lakra R, Rajaram R, Korrapati PS. Development and characterization of zein-based micro carrier system for sustained delivery of aceclofenac sodium. AAPS PharmSciTech. 2011;13:143–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Karthikeyan K, Guhathakarta S, Rajaram R, Korrapati PS. Electrospun zein/eudragit nanofibers based dual drug delivery system for the simultaneous delivery of aceclofenac and pantoprazole. Int J Pharm. 2012;438:117–22.PubMedCrossRefGoogle Scholar
  31. 31.
    Huang W, Zou T, Li S, Jing J, Xia X, Liu X. Drug-loaded zein nanofibers prepared using a modified coaxial electrospinning process. AAPS PharmSciTech. 2013;14:675–81.PubMedCrossRefGoogle Scholar
  32. 32.
    Fernandez A, Torres-Giner S, Lagaron JM. Novel route to stabilization of bioactive antioxidants by encapsulation in electrospun fibers of zein prolamine. Food Hydrocoll. 2009;23:1427–32.CrossRefGoogle Scholar
  33. 33.
    Yang J-M, Zha L-S, Yu D-G, Liu J. Coaxial electrospinning with acetic acid for preparing ferulic acid/zein composite fibers with improved drug release profiles. Colloids Surf B Biointerfaces. 2013;102:737–43.PubMedCrossRefGoogle Scholar
  34. 34.
    Torres-Giner S, Ocio MJ, Lagaron JM. Novel antimicrobial ultrathin structures of zein/chitosan blends obtained by electrospinning. Carbohyd Polym. 2009;77:261–6.CrossRefGoogle Scholar
  35. 35.
    Jiang Q, Yang Y. Water-stable electrospun zein fibers for potential drug delivery. J Biomater Sci Polym Ed. 2011;22:1393–408.CrossRefGoogle Scholar
  36. 36.
    Jiang Y-N, Mo H-Y, Yu D-G. Electrospun drug-loaded core–sheath PVP/zein nanofibers for biphasic drug release. Int J Pharm. 2012;438:232–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Holden MTG, Feil EJ, Lindsay JA, Peacock SJ, Day NPJ, Enright MC, et al. Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc Natl Acad Sci U S A. 2004;101:9786–91.PubMedCrossRefGoogle Scholar
  38. 38.
    Boyle VJ, Fancher ME, Ross RW. Rapid, modified Kirby–Bauer susceptibility test with single, high-concentration antimicrobial disks. Antimicrob Agents Chemother. 1973;3:418–24.PubMedCrossRefGoogle Scholar
  39. 39.
    Li M, Mondrinos MJ, Gandhi MR, Ko FK, Weiss AS, Lelkes PI. Electrospun protein fibers as matrices for tissue engineering. Biomaterials. 2005;26:5999–6008.PubMedCrossRefGoogle Scholar
  40. 40.
    Teo WE, He W, Ramakrishna S. Electrospun scaffold tailored for tissue-specific extracellular matrix. Biotechnol J. 2006;1:918–29.PubMedCrossRefGoogle Scholar
  41. 41.
    Xu W, Karst D, Yang W, Yang Y. Novel zein-based electrospun fibers with the water stability and strength necessary for various applications. Polym Int. 2008;57:1110–7.CrossRefGoogle Scholar
  42. 42.
    Li Y, Lim LT, Kakuda Y. Electrospun zein fibers as carriers to stabilize (−)-epigallocatechin gallate. J Food Sci. 2009;74:C233–40.PubMedCrossRefGoogle Scholar
  43. 43.
    Jiang Q, Reddy N, Yang Y. Cytocompatible cross-linking of electrospun zein fibers for the development of water-stable tissue engineering scaffolds. Acta Biomater. 2010;6:4042–51.PubMedCrossRefGoogle Scholar
  44. 44.
    Reddy N, Yang Y. Potential of plant proteins for medical applications. Trends Biotechnol. 2011;29:490–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Sung HW, Huang RN, Huang L, Tsai CC, Chiu CT. Feasibility study of a natural crosslinking reagent for biological tissue fixation. J Biomed Mater Res. 1998;42:560–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Zhong S, Teo WE, Zhu X, Beuerman R, Ramakrishna S, Yung LYL. Formation of collagen–glycosaminoglycan blended nanofibrous scaffolds and their biological properties. Biomacromolecules. 2005;6:2998–3004.PubMedCrossRefGoogle Scholar
  47. 47.
    Lee J, Edwards H, Pereira C, Samii S. Crosslinking of tissue-derived biomaterials in 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). J Mater Sci Mater Med. 1996;7:531–41.CrossRefGoogle Scholar
  48. 48.
    Qiu W, Cappello J, Wu X. Autoclaving as a chemical-free process to stabilize recombinant silk-elastinlike protein polymer nanofibers. Appl Phys Lett. 2011;98:263702–23.PubMedCrossRefGoogle Scholar
  49. 49.
    Yao C, Li X, Song T. Electrospinning and crosslinking of zein nanofiber mats. J Appl Polym Sci. 2006;103:380–5.CrossRefGoogle Scholar
  50. 50.
    He W, Yong T, Teo WE, Ma Z, Ramakrishna S. Fabrication and endothelialization of collagen-blended biodegradable polymer nanofibers: potential vascular graft for blood vessel tissue engineering. Tissue Eng. 2005;11:1574–88.PubMedCrossRefGoogle Scholar
  51. 51.
    Dash TK, Konkimalla VB. Poly-ε-caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Release. 2012;158:15–33.PubMedCrossRefGoogle Scholar
  52. 52.
    Collins G, Federici J, Imura Y, Catalani LH. Charge generation, charge transport, and residual charge in the electrospinning of polymers: a review of issues and complications. J Appl Phys. 2012;111:044701.CrossRefGoogle Scholar
  53. 53.
    Torres-Giner S, Gimenez E, Lagaron JM. Characterization of the morphology and thermal properties of zein prolamine nanostructures obtained by electrospinning. Food Hydrocoll. 2008;22:601–14.CrossRefGoogle Scholar

Copyright information

© Controlled Release Society 2013

Authors and Affiliations

  • Nour Alhusein
    • 1
  • Ian S. Blagbrough
    • 1
  • Paul A. De Bank
    • 1
    Email author
  1. 1.Department of Pharmacy and PharmacologyUniversity of BathBathUK

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