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Bacterial nanocellulose: the future of controlled drug delivery?

    Yvette Pötzinger

    Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Otto-Schott-Strasse 41, 07745 Jena, Germany

    ,
    Dana Kralisch

    Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Otto-Schott-Strasse 41, 07745 Jena, Germany

    Jena Center for Soft Matter (JCSM), Friedrich-Schiller-University Jena, Philosophenweg 7, 07743 Jena, Germany

    &
    Dagmar Fischer

    *Author for correspondence: Tel.: +49 3641 949 941; Fax: +49 3641 949 942;

    E-mail Address: dagmar.fischer@uni-jena.de

    Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Otto-Schott-Strasse 41, 07745 Jena, Germany

    Jena Center for Soft Matter (JCSM), Friedrich-Schiller-University Jena, Philosophenweg 7, 07743 Jena, Germany

    Published Online:https://doi.org/10.4155/tde-2017-0059

    Although bacterial nanocellulose (BNC), a natural nanostructured biopolymer network, offers unique material characteristics, the number of drug-loaded BNC-based carriers in clinical trials or on the market is still low. This report provides an overview of aspects still limiting the broad application of BNC as drug-delivery system and the challenges for its future applications. Continuous large-scale production, storability, the loading and controlled release of critical drugs, for example, with high molar mass or highly lipophilic character as well as the formulation of long-term release systems will be highlighted. Recent achievements toward promoting the application of BNC as drug-delivery system and overcoming these obstacles will be discussed.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Klemm D, Kramer F, Moritz S et al. Nanocelluloses: a new family of nature-based materials. Angew. Chem. Int. Ed. 50(24), 5438–5466 (2011). •• Provides an overview about modifications and applications of nanocelluloses.
    • 2 Duran N, Lemes AP, Seabra AB. Review of cellulose nanocrystals patents: preparation, composites and general applications. Recent. Pat. Nanotech. 6(1), 16–28 (2012).
    • 3 Schlufter K, Schmauder H-P, Dorn S, Heinze T. Efficient homogeneous chemical modification of bacterial cellulose in the ionic liquid 1-N-Butyl-3-methylimidazolium chloride. Macromol. Rapid. Comm. 27(19), 1670–1676 (2006).
    • 4 Barud HS, Ribeiro CA, Crespi MS et al. Thermal characterization of bacterial cellulose–phosphate composite membranes. J. Therm. Anal. Calorim. 87(3), 815–818 (2007).
    • 5 Lin N, Dufresne A. Nanocellulose in biomedicine: current status and future prospect. Eur. Polym. J. 59, 302–325 (2014).
    • 6 Jeong SI, Lee SE, Yang H, Jin Y-H, Park C-S, Park YS. Toxicologic evaluation of bacterial synthesized cellulose in endothelial cells and animals. Mol. Cell. Toxicol. 6(4), 370–377 (2010).
    • 7 Helenius G, Backdahl H, Bodin A, Nannmark U, Gatenholm P, Risberg B. In vivo biocompatibility of bacterial cellulose. J. Biomed. Mater. Res. A. 76(2), 431–438 (2006).
    • 8 Schumann DA, Wippermann J, Klemm DO et al. Artificial vascular implants from bacterial cellulose: preliminary results of small arterial substitutes. Cellulose 16(5), 877–885 (2009).
    • 9 Almeida IF, Pereira T, Silva NHCS et al. Bacterial cellulose membranes as drug-delivery systems: an in vivo skin compatibility study. Eur. J. Pharm. Biopharm. 86(3), 332–336 (2014). • Presents a clinical study about the use of bacterial nanocellulose (BNC) for skin applications.
    • 10 Frost & Sullivan. Emerging applications of nanocellulose technology. https://store.frost.com/emerging-applications-of-nanocellulose-technology.html.
    • 11 Mosti G, Mattaliano V, Schmitz M. New antimicrobial wound dressing with polyhexanide Suprasorb® X + PHMB, first in vitro and clinical results. Presented at: Annual Congress of the German Society for Wound Healing and Wound Care. Berlin, Germany, 9–10 March 2007.
    • 12 Bruckner M, Schwarz C, Otto F, Heillinger J, Wild T. Evaluation of cellulose and polyhexamethylene biguanide (Suprasorb® X+PHMB) in therapy of infected wounds. EWMA J. (Suppl.) 8(2), 54 (2008).
    • 13 Bowil Biotech Sp. z o.o. www.bowil.pl.
    • 14 Silva NHCS, Rodrigues AF, Almeida IF et al. Bacterial cellulose membranes as transdermal delivery systems for diclofenac: in vitro dissolution and permeation studies. Carbohyd. Polym. 106, 264–269 (2014).
    • 15 Moritz S, Wiegand C, Wesarg F et al. Active wound dressings based on bacterial nanocellulose as drug-delivery system for octenidine. Int. J. Pharm. 471(1–2), 45–55 (2014).
    • 16 Trovatti E, Freire CS, Pinto PC et al. Bacterial cellulose membranes applied in topical and transdermal delivery of lidocaine hydrochloride and ibuprofen: in vitro diffusion studies. Int. J. Pharm. 435(1), 83–87 (2012).
    • 17 Ullah H, Santos HA, Khan T. Applications of bacterial cellulose in food, cosmetics and drug delivery. Cellulose 23(4), 2291–2314 (2016). •• Presents a summary of drugs incorporated into BNC.
    • 18 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(10), 245 (2015).
    • 19 Ahmad N, Amin MCIM, Mahali SM, Ismail I, Chuang VTG. Biocompatible and mucoadhesive bacterial cellulose-g-poly(acrylic acid) hydrogels for oral protein delivery. Mol. Pharm. 11(11), 4130–4142 (2014).
    • 20 Müller A, Ni Z, Hessler N et al. The biopolymer bacterial nanocellulose as drug-delivery system: investigation of drug loading and release using the model protein albumin. J. Pharm. Sci. 102(2), 579–592 (2013).
    • 21 Sampaio LMP, Padrão J, Faria J et al. Laccase immobilization on bacterial nanocellulose membranes: antimicrobial, kinetic and stability properties. Carbohyd. Polym. 145, 1–12 (2016).
    • 22 Wu S-C, Wu S-M, Su F-M. Novel process for immobilizing an enzyme on a bacterial cellulose membrane through repeated absorption. J. Chem. Technol. Biotechnol. 92(1), 109–114 (2017).
    • 23 Ullah H, Badshah M, Mäkilä E et al. Fabrication, characterization and evaluation of bacterial cellulose-based capsule shells for oral drug delivery. Cellulose 1–10 (2017).
    • 24 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 1(23), 2976–2984 (2013).
    • 25 Yoshino A, Tabuchi M, Uo M et al. Applicability of bacterial cellulose as an alternative to paper points in endodontic treatment. Acta Biomater. 9(4), 6116–6122 (2013).
    • 26 Rouabhia M, Asselin J, Tazi N, Messaddeq Y, Levinson D, Zhang Z. Production of biocompatible and antimicrobial bacterial cellulose polymers functionalized by RGDC grafting groups and gentamicin. ACS Appl. Mater. Inter. 6(3), 1439–1446 (2014).
    • 27 Liyaskina E, Revin V, Paramonova E et al. Nanomaterials from bacterial cellulose for antimicrobial wound dressing. J. Phys. Conf. Ser. 784(1), 012034 (2017).
    • 28 Shao W, Liu H, Wang S et al. Controlled release and antibacterial activity of tetracycline hydrochloride-loaded bacterial cellulose composite membranes. Carbohyd. Polym. 145, 114–120 (2016).
    • 29 Shi X, Zheng Y, Wang G, Lin Q, Fan J. pH- and electro-response characteristics of bacterial cellulose nanofiber/sodium alginate hybrid hydrogels for dual controlled drug delivery. RSC Adv. 4(87), 47056–47065 (2014).
    • 30 Trovatti E, Silva NH, Duarte IF et al. Biocellulose membranes as supports for dermal release of lidocaine. Biomacromolecules 12(11), 4162–4168 (2011).
    • 31 Cacicedo ML, Cesca K, Bosio VE, Porto LM, Castro GR. Self-assembly of carrageenin–CaCO3 hybrid microparticles on bacterial cellulose films for doxorubicin sustained delivery. J. Appl. Biomed. 13(3), 239–248 (2015).
    • 32 Müller A, Wesarg F, Hessler N, Müller FA, Kralisch D, Fischer D. Loading of bacterial nanocellulose hydrogels with proteins using a high-speed technique. Carbohyd. Polym. 106, 410–413 (2014).
    • 33 Mohite BV, Suryawanshi RK, Patil SV. Study on the drug loading and release potential of bacterial cellulose. Cell. Chem. Technol. 50(2), 219–223 (2016).
    • 34 Alkhatib Y, Dewaldt M, Moritz S, Nitzsche R, Kralisch D, Fischer D. Controlled extended octenidine release from a bacterial nanocellulose/poloxamer hybrid system. Eur. J. Pharm. Biopharm. 112, 164–176 (2017). •• First description of BNC for the use as long-term release systems for antiseptics.
    • 35 Aramwit P, Bang N. The characteristics of bacterial nanocellulose gel releasing silk sericin for facial treatment. BMC Biotechnol. 14, 104 (2014).
    • 36 Cacicedo ML, León IE, Gonzalez JS, Porto LM, Alvarez VA, Castro GR. Modified bacterial cellulose scaffolds for localized doxorubicin release in human colorectal HT-29 cells. Colloid. Surface. B 140, 421–429 (2016).
    • 37 Li J, Wan Y, Li L, Liang H, Wang J. Preparation and characterization of 2,3-dialdehyde bacterial cellulose for potential biodegradable tissue engineering scaffolds. Mater. Sci. Eng. C 29(5), 1635–1642 (2009).
    • 38 Hu W, Chen S, Yang J, Li Z, Wang H. Functionalized bacterial cellulose derivatives and nanocomposites. Carbohyd. Polym. 101, 1043–1060 (2014).
    • 39 Alosmanov R, Wolski K, Zapotoczny S. Grafting of thermosensitive poly(N-isopropylacrylamide) from wet bacterial cellulose sheets to improve its swelling-drying ability. Cellulose 24(1), 285–293 (2017).
    • 40 Pavaloiu R-D, Stoica-Guzun A, Dobre T. Swelling studies of composite hydrogels based on bacterial cellulose and gelatin. U.P.B. Sci. Bull. Ser. B 77(1), 53–62 (2015).
    • 41 Pavaloiu R-D, Stoica-Guzun A, Stroescu M, Jinga SI, Dobre T. Composite films of poly(vinyl alcohol)–chitosan–bacterial cellulose for drug controlled release. Int. J. Biol. Macromol. 68, 117–124 (2014).
    • 42 Numata Y, Mazzarino L, Borsali R. A slow-release system of bacterial cellulose gel and nanoparticles for hydrophobic active ingredients. Int. J. Pharm. 486(1–2), 217–225 (2015).
    • 43 Luo H, Ao H, Li G et al. Bacterial cellulose/graphene oxide nanocomposite as a novel drug-delivery system. Curr. Appl. Phys. 17(2), 249–254 (2017).
    • 44 Sukhtezari S, Almasi H, Pirsa S, Zandi M, Pirouzifard M. Development of bacterial cellulose based slow-release active films by incorporation of Scrophularia striata Boiss extract. Carbohyd. Polym. 156, 340–350 (2017). • Description of using cyclodextrins as carrier in BNC for poorly soluble substances.
    • 45 Berndt S, Wesarg F, Wiegand C, Kralisch D, Müller FA. Antimicrobial porous hybrids consisting of bacterial nanocellulose and silver nanoparticles. Cellulose 20(2), 771–783 (2013).
    • 46 Khalid A, Khan R, Ul-Islam M, Khan T, Wahid F. Bacterial cellulose-zinc oxide nanocomposites as a novel dressing system for burn wounds. Carbohyd. Polym. 164, 214–221 (2017).
    • 47 Scholz P, Müller A, Heßler N, Kralisch D, Fischer D. Freeze dried bacterial nanocellulose as potential drug-delivery system for peroral application of sensitive drugs. Presented at: CRS Local German Chapter Annual Meeting. Würzburg, Germany, 29–30 March 2012.
    • 48 Phisalaphong M, Tran T-K, Taokaew S et al. Nata de coco industry in Vietnam, Thailand, and Indonesia. In: Bacterial Nanocellulose – From Biotechnology to Bio-Economy. Gama M, Dourado F, Bielecki S (Eds). Elsevier, Amsterdam, The Netherlands, 231–236 (2016).
    • 49 Piazodo MES. Nata de coco industry in the Philippines. In: Bacterial Nanocellulose – From Biotechnology to Bio-Economy. Gama M, Dourado F, Bielecki S (Eds). Elsevier, Amsterdam, The Netherlands, 215–229 (2016).
    • 50 Kralisch D, Hessler N, Klemm D, Erdmann R, Schmidt W. White biotechnology for cellulose manufacturing – the HoLiR concept. Biotechnol. Bioeng. 105(4), 740–747 (2010). •• First description of a (semi-)continuous upscale of BNC production.
    • 51 Wu SC, Li MH. Production of bacterial cellulose membranes in a modified airlift bioreactor by Gluconacetobacter xylinus. J. Biosci. Bioeng. 120(4), 444–449 (2015).
    • 52 Lee KY, Buldum G, Mantalaris A, Bismarck A. More than meets the eye in bacterial cellulose: biosynthesis, bioprocessing, and applications in advanced fiber composites. Macromol. Biosci. 14(1), 10–32 (2014).
    • 53 Zeng M, Laromaine A, Roig A. Bacterial cellulose films: influence of bacterial strain and drying route on film properties. Cellulose 21(6), 4455–4469 (2014).
    • 54 Qiu Y, Qiu L, Cui J, Wei Q. Bacterial cellulose and bacterial cellulose-vaccarin membranes for wound healing. Mater. Sci. Eng. C. Mater. Biol. Appl. 59, 303–309 (2016).
    • 55 Müller A, Zink M, Hessler N et al. Bacterial nanocellulose with a shape-memory effect as potential drug-delivery system. RSC Adv. 4(100), 57173–57184 (2014).
    • 56 Kaplan E, Ince T, Yorulmaz E, Yener F, Harputlu E, Laçin NT. Controlled delivery of ampicillin and gentamycin from cellulose hydrogels and their antibacterial efficiency. J. Biomater. Tiss. Eng. 4(7), 543–549(547), (2014).