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Antimicrobial functionalization of bacterial nanocellulose by loading with polihexanide and povidone-iodine

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Abstract

Bacterial nanocellulose (BNC) is chemically identical with plant cellulose but free of byproducts like lignin, pectin, and hemicelluloses, featuring a unique reticulate network of fine fibers. BNC sheets are mostly obtained by static cultivation. Now, a Horizontal Lift Reactor may provide a cost efficient method for mass production. This is of particular interest as BNC features several properties of an ideal wound dressing although it exhibits no bactericidal activity. Therefore, BNC was functionalized with the antiseptics povidone-iodine (PI) and polihexanide (PHMB). Drug loading and release, mechanical characteristics, biocompatibility, and antimicrobial efficacy were investigated. Antiseptics release was based on diffusion and swelling according to Ritger–Peppas equation. PI-loaded BNC demonstrated a delayed release compared to PHMB due to a high molar drug mass and structural changes induced by PI insertion into BNC that also increased the compressive strength of BNC samples. Biological assays demonstrated high biocompatibility of PI-loaded BNC in human keratinocytes but a distinctly lower antimicrobial activity against Staphylococcus aureus compared to PHMB-loaded BNC. Overall, BNC loaded with PHMB demonstrated a better therapeutic window. Moreover, compressive and tensile strength were not changed by incorporation of PHMB into BNC, and solidity during loading and release could be confirmed.

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Abbreviations

AATCC:

American Association of Textile Chemists and Colorists

BNC:

Bacterial nanocellulose

cBNC:

Cut BNC samples

DMEM:

Dulbecco’s modified Eagle medium

HoLiR:

Horizontal Lift Reactor

IC50 :

Half maximal inhibitory concentration

LC50 :

Half maximal lethal concentration

MLN:

Microplate laser nephelometry

pBNC:

24-well-plate BNC samples

PHMB:

Polihexanide

PI:

Povidone-iodine

References

  1. Jonas R, Farah LF. Production and application of microbial cellulose. Poly Deg Stab. 1998;59:101–6.

    Article  Google Scholar 

  2. Borzani W, De Souza SJ. Mechanism of the film thickness increasing during bacterial production of cellulose in non-agitated liquid media. Biotechnol Lett. 1995;17:1271–2.

    Article  Google Scholar 

  3. El-Saied H, El-Diwany AI, Basta AH, Atwa NA, El-Ghwas DE. Production and characterization of economical bacterial cellulose. Bioresources. 2008;3:1196–217.

    Google Scholar 

  4. Czaja W, Krystynowicz A, Bielecki S, Brown RM Jr. Microbial cellulose—the natural power to heal wounds. Biomaterials. 2006;27:145–51.

    Article  Google Scholar 

  5. Czaja W, Young DJ, Kawecki M, Brown RM Jr. The future prospects of microbial cellulose in biomedical applications. Biomacromol. 2007;8:1–12.

    Article  Google Scholar 

  6. Fontana JD, DeSouza AM, Fontana CK, Torriani IL, Moreschi JC, Gallotti BJ, DeSouza SJ, Narcisco GP, Bichara JA, Farah LFX. Acetobacter cellulose pellicle as a temporary skin substitute. Appl Biochem Biotechnol. 1990;24–25:253–64.

    Article  Google Scholar 

  7. Rebello C, Almeida DAD, Lima EM Jr, Dornelas MDP. Biofill a new skin substitute: our experience. Rev Bras Cir. 1987;77:407–14.

    Google Scholar 

  8. Warriner R, Burrel RE. Infection and the chronic wound: a focus on silver. Adv Skin Wound Care. 2005;18:2–12.

    Article  Google Scholar 

  9. Wright JB, Lam K, Buret AG, Olson ME, Burrell RE. Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing. Wound Rep Reg. 2002;10:141–51.

    Article  Google Scholar 

  10. Berndt S, Wesarg F, Wiegand C, Kralisch D, Müller F. Antimicrobial porous hybrids consisting of bacterial nanocellulose and silver nanoparticles. Cellulose. 2013;20:771–83.

    Article  Google Scholar 

  11. Müller A, Ni Z, Hessler N, Wesarg F, Müller FA, Kralisch D, Fischer D. The biopolymer bacterial nanocellulose as drug delivery system: investigation of drug loading and release using the model protein albumin. J Pharm Sci. 2013;102:579–92.

    Article  Google Scholar 

  12. Jipa IM, Stoica A, Stroescu M, Dobre LM, Dobre T, Jinga S, Tardei C. Potassium sorbate release from poly(vinyl alcohol)-bacterial cellulose films. Chem Pap. 2012;66:138–43.

    Article  Google Scholar 

  13. Mori R, Nakai T, Enomoto K, Uchio Y, Yoshino K. Increased antibiotic release from a bone cement containing bacterial cellulose. Clin Orthop Relat Res. 2011;469:600–6.

    Article  Google Scholar 

  14. Trovatti E, Silva NHCS, Duarte IF, Rosado CF, Almeida IF, Costa P, Freire CSR, Silvestre AJD, Pascoal NC. Biocellulose membranes as supports for dermal release of lidocaine. Biomacromol. 2011;12:4162–8.

    Article  Google Scholar 

  15. Bodhibukkana C, Srichana T, Kaewnopparat S, Tangthong N, Bouking P, Martin GP, Suedee R. Composite membrane of bacterially-derived cellulose and molecularly imprinted polymer for use as a transdermal enantioselective controlled-release system of racemic propranolol. J Controlled, Release. 2006;113:43–56.

    Article  Google Scholar 

  16. Yang G, Xie J, Hong F, Cao Z, Yang X. Antimicrobial activity of silver nanoparticle impregnated bacterial cellulose membrane: effect of fermentation carbon sources of bacterial cellulose. Carbohydr Polym. 2012;87:839–45.

    Article  Google Scholar 

  17. Maneerung T, Tokura S, Rujiravanit R. Impregnation of silver nanoparticles into bacterial cellulose for antimicrobial wound dressing. Carbohydr Polym. 2008;72:43–51.

    Article  Google Scholar 

  18. Wiegand C, Heinze T, Hipler UC. Comparative in vitro study on cytotoxicity, antimicrobial activity, and binding capacity for pathophysiological factors in chronic wounds of alginate and silver-containing alginate. Wound Rep Reg. 2009;17:511–21.

    Article  Google Scholar 

  19. Ip M, Lui SL, Poon VKM, Lung I, Burd A. Antimicrobial activities of silver dressings: an in vitro comparison. J Med Microbiol. 2006;55:59–63.

    Article  Google Scholar 

  20. Hidalgo E, Bartolome R, Barroso C, Moreno A, Dominguez C. Silver nitrate: antimicrobial activity related to cytotoxicity in cultured human fibroblasts. Skin Pharmacol Appl Skin Physiol. 1998;11:140–51.

    Article  Google Scholar 

  21. Moritz S, Wiegand C, Wesarg F, Hessler N, Müller FA, Kralisch D, Hipler UC, Fischer D. Active wound dressings based on bacterial nanocellulose as drug delivery system for octenidine. Int J Pharm. 2014;471:45–55.

    Article  Google Scholar 

  22. Wei B, Yang G, Hong F. Preparation and evaluation of a kind of bacterial cellulose dry films with antibacterial properties. Carbohydr Polym. 2011;84:533–8.

    Article  Google Scholar 

  23. Zheng Y, Wu J, Peng S, Guo J, Yang H, Xi T, Fei H, He X, Liu X. Preparation of silver sulfadiazine/bacterial cellulose composite membranes as antibacterial wound dressing for controlling burn or scald wound infections. Beijing: University of Science and Technology Beijing; 2010. p. 12.

    Google Scholar 

  24. Kralisch D, Hessler N, Klemm D, Erdmann R, Schmidt W. White biotechnology for cellulose manufacturing-The HoLiR concept. Biotechnol Bioeng. 2009;105:740–7.

    Google Scholar 

  25. Niazi SN. Handbook of pharmaceutical manufacturing formulations liquid products. 2nd ed. Boca Raton: CRC Press; 2009.

    Book  Google Scholar 

  26. Küsters M, Beyer S, Kutscher S, Schlesinger H, Gerhartz M. Rapid, simple and stability-indicating determination of polyhexamethylene biguanide in liquid and gel-like dosage forms by liquid chromatography with diode-array detection. J Pharmaceut Anal. 2013;3:408–14.

    Google Scholar 

  27. Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Controlled Release. 1987;5:37–42.

    Article  Google Scholar 

  28. Wiegand C, Hipler UC. Evaluation of biocompatibility and cytotoxicity using keratinocyte and fibroblast cultures. Skin Pharmacol Physiol. 2009;22:74–82.

    Article  Google Scholar 

  29. Wiegand C, Abel M, Ruth P, Hipler UC. HaCaT keratinocytes in co-culture with Staphylococcus aureus can be protected from bacterial damage by polihexanide. Wound Rep Reg. 2009;17:730–8.

    Article  Google Scholar 

  30. Amari H, Lari L, Zhang HY, Geelhaar L, Chèze C, Kappers MJ, McAleese C, Humphreys CJ, Walther T. Accurate calibration for the quantification of the Al content in AlGaN epitaxial layers by energy-dispersive X-ray spectroscopy in a transmission electron microscope. J Phys: Conf Ser. 2011;326:012028.

    Google Scholar 

  31. Chiaoprakobkij N, Sanchavanakit N, Subbalekha K, Pavasant P, Phisalaphong M. Characterization and biocompatibility of bacterial cellulose/alginate composite sponges with human keratinocytes and gingival fibroblasts. Carbohydr Polym. 2011;85:548–53.

    Article  Google Scholar 

  32. Sanchavanakit N, Sangrungraungroj W, Kaomongkolgit R, Banaprasert T, Pavasant P, Phisalaphong M. Growth of human keratinocytes and fibroblasts on bacterial cellulose film. Biotechnol Prog. 2006;22:1194–9.

    Article  Google Scholar 

  33. Reimer K, Wichelhaus TA, Schäfer V, Rudolph P, Kramer A, Wutzler P, Ganzer D, Fleischer W. Antimicrobial effectiveness of povidone-iodine and consequences for new applications. Dermatology. 2002;204(Suppl1):114–20.

    Article  Google Scholar 

  34. Wiegand C, Abel M, Ruth P, Hipler UC. Analysis of the adaptation capacity of Staphylococcus aureus to commonly used antiseptics by microplate laser nephelometry. Skin Pharmacol Physiol. 2012;25:288–97.

    Article  Google Scholar 

  35. Kunisada T, Yamada K, Oda S, Hara O. Investigation on the efficacy of povidone-iodine against antiseptic-resistant species. Dermatol. 1997;195(Suppl2):14–8.

    Article  Google Scholar 

  36. Hirsch T, Jacobsen F, Rittig A, Goertz O, Niederbichler A, Steinau HG, Seipp HM, Steintraesser L. Vergleichende In-vitro-Studie zur Zytotoxizität klinisch eingesetzter Antiseptika. Hautarzt. 2009;60:984–91.

    Article  Google Scholar 

  37. Daeschlein G, Assadian O, Bruck JC, Meinl C, Kramer A, Koch S. Feasibility and clinical applicability of polihexanide for treatment of second-degree burn wounds. Skin Pharmacol Physiol. 2007;20:292–6.

    Article  Google Scholar 

  38. Wilhelms T, Schulze D, Alupeil C, Rohrer C, Abel M, Wiegand C, Hipler UC. Release of polyhexamethylene biguanide hydrochloride (PHMB) from a hydrobalanced cellulose wound dressing with PHMB. In: 17th Conference of the European Wound Management Association, Glasgow/UK; 2007.

  39. Calabrese VT, Khan A. Polyiodine and polyiodide species in an aqueous solution of iodine + KI. Theoretical and experimental studies. J Phys Chem A. 2000;104:1287–92.

    Article  Google Scholar 

  40. Gazda DB, Lipert RJ, Fritz JS, Porter MD. Investigation of the iodine-poly(vinylpyrrolidone) interaction employed in the determination of biocidal iodine by colorimetric solid-phase extraction. Anal Chim Acta. 2004;510:241–7.

    Article  Google Scholar 

  41. Garg S, Jambu L, Vermani K. Development of novel sustained release bioadhesive vaginal tablets of povidone iodine. Drug Dev Ind Pharm. 2007;33:1340–9.

    Article  Google Scholar 

  42. Silva NHCS, Rodrigues AF, Almeida IF, Costa PC, Rosado C, Neto CP, Silvestre AJD, Freire CSR. Bacterial cellulose membranes as transdermal delivery systems for diclofenac: in vitro dissolution and permeation studies. Carbohydr Polym. 2014;106:264–9.

    Article  Google Scholar 

  43. Huang L, Chen X, Nguyen TX, Tang H, Zhang L, Yang G. Nano-cellulose 3D-networks as controlled-release drug carriers. J Mater Chem B. 2013;1:2976–84.

    Article  Google Scholar 

  44. McDonnel G, Russel AD. Antiseptics and disinfectants: activity, action and resistance. Clin Microbiol Rev. 1999;12(1):147–79.

    Google Scholar 

  45. Müller G, Koburger T, Jethon FUW, Kramer A. Vergleich der bakterioziden Wirksamkeit und In-vitro-Zytotoxizität von Lavasept und Prontosan. GMS Krankenhaushyg Interdiszip. 2007;2(2):doc42.

    Google Scholar 

  46. Müller G, Kramer A. Biocompatibility index of antiseptic agents by parallel assessment of antimicrobial activity and cellular cytotoxicity. J Antimic Chemther. 2008;61:1281–7.

    Article  Google Scholar 

  47. Kramer A, Roth B, Müller G, Rudolph P, Klöcker N. Influence of the antiseptic agents polyhexanide and octenidine on FL Cells and on healing of experimental superficial aseptic wounds in piglets. Skin Pharmacol Physiol. 2004;17:141–6.

    Article  Google Scholar 

  48. Wiegand C, Abel M, Kramer A, Müller G, Ruth P, Hipler UC. Proliferationsförderung und Biokompatibilität von Polihexanid. GMS Krankenhaushyg Interdiszip. 2007;2(2):doc43.

    Google Scholar 

  49. VantocilTM IB Antimicrobial. Technical information bulletin. Cheschire: Arch Chemicals Inc; 2005.

    Google Scholar 

  50. Bunting TG, Sackler RS, Centrone DA, Halpern A. Irradiation of poly(vinylpyrrolidone) and its iodine complex. DE3319019A1; 1983.

  51. Barabas ES, Brittain HG. Povidone-Iodine. In: Harry GB, editor. Analytical profiles of drug substances and excipients. San Diego: Academic Press; 1998. p. 341–462.

    Chapter  Google Scholar 

  52. Bühler V. Generic drug formulations. Ludwigshafen: BASF Fine Chemicals Generic Drug Formulations; 1998.

    Google Scholar 

  53. Wesarg F, Schlott F, Grabow J, Kurland HD, Hessler N, Kralisch D, Müller FA. In situ synthesis of photocatalytically active hybrids consisting of bacterial nanocellulose and anatase nanoparticles. Langmuir. 2012;28:13518–25.

    Article  Google Scholar 

  54. Bäckdahl H, Helenius G, Bodin A, Nannmark U, Johansson BR, Risberg B, Gatenholm P. Mechanical properties of bacterial cellulose and interactions with smooth muscle cells. Biomaterials. 2006;27:2141–9.

    Article  Google Scholar 

  55. de Paula GF, Netto GI, Mattoso LHC. Physical and chemical characterization of poly(hexamethylene biguanide) hydrochloride. Polymers. 2011;3:928–41.

    Article  Google Scholar 

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Acknowledgments

The authors would like to thank Ramona Brabetz, Elena Pfaff, and Denise Reichmann for their excellent technical assistance.

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Correspondence to Cornelia Wiegand.

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Conflicts of interest

All authors (NanocellCare) gratefully acknowledge the Thuringian Ministry of Education, Science and Culture and the European Fund for Regional Development (B714-10032). S.M. is grateful to the FAZIT Foundation, Gemeinnützige Verlagsgesellschaft mbH for financial support. Otherwise the authors declare that they have no conflict of interest.

Research involving human participants and/or animals

The work presented here did not involve human participants and/or animals.

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Cornelia Wiegand and Sebastian Moritz have contributed equally to this work.

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Wiegand, C., Moritz, S., Hessler, N. et al. Antimicrobial functionalization of bacterial nanocellulose by loading with polihexanide and povidone-iodine. J Mater Sci: Mater Med 26, 245 (2015). https://doi.org/10.1007/s10856-015-5571-7

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